The localization of the bone lesions of Paget's disease by radiographs, scintigraphy and thermography: pain may be related to bone blood flow.
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Bone and Bones↗
Biomedical subjects
M Smith
Publications and source records attributed to M Smith.
Milk lactose, citrate, and glucose as markers of lactogenesis in normal and diabetic women.
A study was undertaken to define an appropriate marker of lactogenesis II (the onset of copious milk secretion) in mothers, and to determine the effect of diabetes on this marker. Changes in the concentrations of three milk components--lactose, citrate, and glucose--were measured in 38 normal mothers and 6 type I diabetic mothers up to 10 days after birth. Milk yield was measured in 12 of the normal mothers, and all mothers were asked to note the time of milk "coming in" (the feeling of overfullness of the breasts). The average concentrations of lactose, citrate, and glucose in milk were low for the first 24 h after birth, then between 24 and 48 h after birth there was a rapid increase in the concentrations of lactose and citrate, and this transitional period was followed by a plateau period that began between 60 and 84 h after birth. For individual mothers the transitional period for citrate began 32 +/- 9 h (n = 13) and finished 77 +/- 10 h (n = 17) after birth, and for lactose the transitional period finished at 53 +/- 12 h (n = 29) after birth. For diabetic mothers these times were significantly later. The average 24-h milk intake by infants increased from 82 to 556 ml/24 h between 24 and 144 h after birth. Milk intakes were correlated with the concentration of lactose (r = 0.52, n = 51, p less than 0.001), citrate (r = 0.47, n = 47, p less than 0.001), and glucose (r = 0.69, n = 50, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Cifenline in the short-term treatment of patients with ventricular premature complexes: a double-blind placebo-controlled study.
To study the efficacy and safety of cifenline (cibenzoline), a new antiarrhythmic agent, we enrolled 46 patients with greater than 700 premature ventricular complexes (VPCs)/24 h in an ambulatory electrocardiography study. During an open-label titration phase, 25 patients showed greater than 75% VPC suppression while receiving 130 mg (15 patients) or 160 mg (10 patients) cifenline twice daily. During a double-blind placebo-controlled phase in 23 of these patients, cifenline was more effective than placebo in controlling VPCs (p less than 0.0001) and VPC pairs (p less than 0.025). A small (0.01 s) increase in QRS duration was observed (p less than 0.05) during cifenline treatment. Adverse experiences included gastrointestinal complaints and dizziness as well as two instances of hypotension and one instance of symptomatic ventricular tachycardia. Cifenline appears to be effective and well tolerated in the treatment of VPCs.
Adult↗
Effect of mineralocorticoids and salt loading on renin release, renal renin content and renal renin mRNA in mice.
1. DOCA and 9 alpha-fludrocortisone were given to mice on a high-sodium diet for periods of up to 20 weeks, resulting in decreases in plasma renin concentration, renal renin concentration and renal renin mRNA with both treatments. 2. Plasma renin concentration was suppressed prior to suppression of renin mRNA and renal renin levels, indicating that suppression of synthesis and secretion of renin occur separately. 3. The decrease in renal renin concentration that occurred with DOCA was greater and more rapid than the decrease that occurred with 9 alpha-fludrocortisone, suggesting that DOCA caused intra-renal breakdown of renin. 4. When DOCA was given to mice on a low-sodium diet, plasma renin concentration and renal renin concentration increased, indicating that the effects of DOCA on renin levels were dependent on dietary sodium. 5. Renin secretion and synthesis appeared to be controlled by different mechanisms and sodium balance has an important effect on both processes.
Animals↗
Subjective bias in reports of poor work adjustment in depressed patients.
Twenty-five depressed inpatients were asked to report their adjustment at work during the 4-month period preceding their hospitalization. Two separate reports were given: the first during the acute illness phase and the second one 10-28 days later, after symptomatic remission following standardized pharmacotherapy. Thirty-two percent more patient ratings showed absence of adjustment problems on the second report compared with the first. Significant differences between the 2 reports were found in 7 of the 9 items on the Structured and Scaled Interview to Assess Maladjustment, which is designed to assess specific aspects of maladjustment at work. The changes in the scores of maladjustment correlated with the changes in the scores of depressive symptoms, and 40% of the variation in maladjustment scores was accounted for by the pessimism item of the Montgomery-Asberg Depression Rating Scale. Much of the poor work adjustment reported by the acutely depressed patients thus seems to be caused by symptom-related subjective bias.
Adult↗
Germination of Clostridium cylindrosporum Spores on Medium Containing Uric Acid.
Clostridium cylindrosporum spores germinated rapidly under reducing conditions when bicarbonate, uric acid, and calcium were present. Germination rates on 10 mM urate increased with increasing Ca (maximum rate at 5 mM Ca or greater). Germination rates on urate (limiting Ca) increased with increasing urate concentrations to 10 mM urate. At 10 mM Ca, germination rates reached a maximum at 1 mM urate and remained constant thereafter. Cations (Na, K, Li, and Mg), purines, purine analogs, and EDTA inhibited germination at limiting calcium concentrations but not (except for 10 mM adenine) at 10 mM Ca. Methyl viologen or formate did not inhibit germination. Germination was not observed in solutions containing xanthine, hypoxanthine, caffeine, theophylline, 6,8-dihydroxypurine, adenine, allopurinol, formate, glycine, or acetate, even though some of the purines are growth substrates.
Journal Article↗
The Epstein-Barr virus BMLF1 promoter contains an enhancer element that is responsive to the BZLF1 and BRLF1 transactivators.
We have previously shown that the Epstein-Barr virus (EBV) immediate-early gene product, BZLF1, can activate expression of the EBV BMLF1 immediate-early promoter in EBV-positive, but not EBV-negative, B cells, suggesting that the BZLF1 effect may be mediated through another EBV gene product (S. Kenney, J. Kamine, E. Holley-Guthrie, J.-C. Lin, E.-C. Mar, and J. S. Pagano, J. Virol. 63:1729-1736, 1989). Here, we show that the EBV BRLF1 immediate-early gene product transactivates the BMLF1 promoter in either EBV-positive or EBV-negative B cells. Deletional analysis revealed that both the BZLF1-responsive region and the BRLF1-responsive region of the BMLF1 promoter are contained within the same 140-base-pair FokI-PvuII fragment located 300 base pairs upstream of the mRNA start site. This FokI-PvuII fragment functions as an enhancer element in the presence of the BRLF1 transactivator and contains the sequence CCGTGGAGA ATGTC, which is strikingly similar to the BRLF1-responsive region of the EBV DR/DL enhancer (A. Chevallier-Greco, H. Gruffat, E. Manet, A. Calender, and A. Sergeant, J. Virol. 63:615-623, 1989). The effect of BZLF1 on the BMLF1 promoter is likely to be indirect and mediated through the BRLF1 transactivator.
Base Sequence↗
Role of intron splicing in the function of the MATa1 gene of Saccharomyces cerevisiae.
The MATa1 gene of Saccharomyces cerevisiae is unique in yeast cells in that it contains two short intervening sequences (IVS1 and IVS2) 54 and 51 nucleotides long. The 3' intron is inefficiently spliced and results in the accumulation of transcript with only the first intron removed, leading to the speculation that the gene may produce different protein products by alternative splicing patterns. We have used in vitro mutagenic techniques to construct intronless MATa1 genes and have introduced point substitutions in the 5'-TACTAAC-3' internal conserved sequence of each intron to identify the protein product that is required for repression of haploid-specific genes. Analysis of these constructs for the ability to repress expression of an HO::lacZ fusion and for the ability to allow diploid cells to undergo sporulation during conditions of starvation revealed that the gene is functional with two, one, or no introns and that the only functional protein is the one produced when both introns are spliced from the mRNA.
Amino Acid Sequence↗
Cassette mutagenic analysis of the yeast invertase signal peptide: effects on protein translocation.
The coding sequence of the SUC2 locus was placed under the control of the constitutive ADH1 promoter and transcription terminator in a centromere-based yeast plasmid vector from which invertase is expressed in a Suc- strain of Saccharomyces cerevisiae. Mutants in the signal peptide sequence were produced by replacing this region of the gene with synthetic oligonucleotide cassettes containing mixtures of nucleotides at several positions. The mutants could be divided into three classes on the basis of the ability to secrete invertase. Class I mutants produced secreted invertase but in reduced amount. The class II mutant, 4-55B, also exhibited reduced a level of invertase, but a significant fraction of the enzyme was intracellular. Class III mutants were partially defective in translocation from the cytoplasm to the endoplasmic reticulum and produced enzymatically active, unglycosylated preinvertase in the cytoplasm. Class III mutant preinvertases were also defective in translocation across canine pancreas microsomes. These results suggested that the reduced level of invertase resulted from proteolytic degradation of inefficiently transported intermediates. Comparison of the sequences of the mutant signal peptides indicated that amino acids at the extreme amino terminus and adjacent to the cleavage site play a crucial role in the secretory process when combined with a mutation within the hydrophobic core.
Amino Acid Sequence↗
Plasma amino acid concentrations in parenterally fed preterm infants.
One hundred and nine sick preterm infants were studied, and the data obtained show that hyperphenylalaninaemia is an extremely rare occurrence as long as an adequate source of energy is provided. High concentrations of the other aromatic amino acid (tyrosine) on the other hand, were often encountered and seem to be due to immaturity of an isolated hepatic enzyme as there was no correlation between phenylalanine and tyrosine concentrations. Possible adverse consequences of hypertyrosinaemia are discussed in relation to toxicity and the assessment of hepatic function. We provide reference centiles for plasma amino acid concentrations in this population.
Amino Acids↗
Identification and characterisation of a small marker chromosome using non-isotopic in situ hybridisation with X and Y specific probes.
A 13 year old male with mild mental retardation, obesity, and poor secondary sexual differentiation was found to have a 46,X,+,mar karyotype. In situ hybridisation with X and Y specific probes proved the marker to be composed of Y centromeric and short arm material.
Adolescent↗
The response of the pulmonary circulation to exercise during normoxia and hypoxia following pneumonectomy in the adult sheep.
Pneumonectomy approximately halves the available pulmonary vascular bed. It is unknown whether the remaining lung has sufficient vascular reserve to cope with increased blood flow under stressful conditions without demonstrating abnormal pulmonary hemodynamics. To investigate this question, unanesthetized ewes with vascular catheters had hemodynamics assessed before and after a left pneumonectomy. Subsequently, on different days, the sheep were exercised on a treadmill under normoxic and hypobaric hypoxic (430 mmHg) (1 mmHg = 133.3 Pa) conditions. Pneumonectomy itself increased mean pulmonary arterial pressure by 4 mmHg. During normoxic or hypoxic exercise, the pneumonectomized sheep demonstrated a pulmonary hemodynamic response similar to normal sheep with two lungs. The pressure-flow relation for the right lung suggested the vascular reserve of the lung was not exceeded during exercise in the pneumonectomized sheep. Eighteen to 70 days after pneumonectomy there was no evidence of right ventricular hypertrophy, but there were small increases in the number of muscularized vessels less than 50 microns diameter and in the amount of muscle in normally muscularized pulmonary arteries. This study demonstrates that pneumonectomy slightly increases mean pulmonary arterial pressure. However, there is sufficient vascular reserve in the remaining lung to permit a normal hemodynamic response to exercise-induced increased blood flow even under hypoxic conditions.
Animals↗
Response of aequorin-loaded platelets to activators of protein kinase C.
The protein kinase C activators phorbol ester 12-myristate 13-acetate (PMA) and 1-oleyl-2-acetylglycerol (DAG) cause platelet aggregation, secretion, and a rise in aequorin-indicated cytoplasmic Ca2+ ([Ca2+]i), but the importance of this action to platelet activation by these agonists has not been established. We found that the previous addition of PMA or DAG either enhanced or inhibited the platelet response if thrombin was subsequently added, depending on the latter's concentration. The effects of PMA or DAG on the response to thrombin were obtained only if the agonists were added in concentrations sufficient to elevate [Ca2+]i themselves. A [Ca2+]i rise also occurred after the second agonist (thrombin), but its magnitude did not necessarily correlate with subsequent aggregation, secretion, or the activation of protein kinase C as reported by the phosphorylation of a 47-kDa protein (p47). The protein kinase C inhibitor sphingosine inhibited aggregation and p47 phosphorylation caused by PMA or DAG alone or with thrombin, but the [Ca2+]i rise in response to the first agonist was not affected. PMA-induced aggregation and p47 phosphorylation were inhibited by quin2, which also inhibited protein kinase C activity in a cell-free system. We conclude that a rise in aequorin-indicated [Ca2+]i is necessary for PMA or DAG to activate platelets or to alter the subsequent platelet response to thrombin; this [Ca2+]i rise may be a prerequisite for activation of protein kinase C.
Aequorin↗
Report of the committee on the genetic constitution of chromosomes 9 and 10.
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Chromosome Mapping↗
Effect of converting enzyme inhibition on renin synthesis and secretion in mice.
We have investigated the relative importance of renal renin stores and de novo synthesis during stimulation of renin secretion and the role of transcription and posttranscriptional factors in providing increased synthesis of renin. When enalapril was administered to previously untreated mice, plasma renin concentration increased 40-fold within 1.5 hours, and remained at a high level for the 8 days of the experiment. Renal renin decreased by 82% after 24 hours and thereafter increased to levels higher than controls. Calculations of renin turnover, based on data for the rate of metabolism of renin in plasma, indicated that most of the renin released in the first 24 hours could be accounted for by the decrease in renal renin stores, indicating that de novo synthesis played only a minor role. After 24 hours, however, when both plasma renin concentration and renal renin increased, the calculated rate of renin synthesis increased to nearly 40 times the rate in controls. When enalapril was administered to mice that had been depleted of plasma and renal renin by chronic sodium loading, plasma renin concentration increased markedly within 1.5 hours, but to only half the level achieved in the previously untreated mice. No decrease in renal renin occurred, suggesting that the renal renin remaining after chronic sodium loading was not available for release. Renal renin messenger RNA increased 4.5-fold after 6 hours, and after 8 days had increased to 5.0 times the level at day 0. The increase in calculated rate of renin synthesis was maximal between 5 and 8 days, when it was 54 times greater than at day 0. During enalapril treatment, there were marked increases in the granulation of the juxtaglomerular cells and in the amount of rough endoplasmic reticulum and Golgi apparatus they contained. These results suggest that posttranscriptional factors play a major role in determining the rate of renin synthesis.
Analysis of Variance↗
Thyroid hormone antibodies and Hashimoto's thyroiditis in mongrel dogs.
Abnormally elevated serum T3 concentrations measured by RIA were observed in 19 clinically euthyroid or hypothyroid mongrel dogs. The serum T4 concentrations in these sera were low, normal, or high. Measurement of the intensity of thyroid hormone binding to serum proteins was determined by equilibrium dialysis. A marked decrease in the percent free T3 was observed in these abnormal sera. Polyacrylamide gel electrophoresis, pH 7.4, of normal dog serum enriched with tracer 125I-labeled thyroid hormones demonstrated binding of [125I]T4 to transthyretin, thyroid hormone-binding globulin, and albumin and of [125I]T3 primarily to thyroid hormone-binding globulin. In all abnormal sera, polyacrylamide gel electrophoresis demonstrated strikingly higher binding of T3 to immunoglobulin (Ig). Eleven of 16 abnormal sera had minimal to moderate binding of T4 to Ig. The percent free T4 was lower only in dogs whose sera demonstrated markedly increased binding of T4 to Ig. All abnormal sera tested had positive antithyroglobulin antibodies, consistent with the diagnosis of autoimmune lymphocytic thyroiditis. As in humans, antibodies to thyroid hormones in dogs are more common in the presence of Hashimoto's thyroiditis and should be considered when elevated serum thyroid hormone concentrations are observed in the absence of clinical thyrotoxicosis. When an antibody to only one thyroid hormone is present, a marked discrepancy in the serum concentrations of T3 and T4 will be observed.
Animals↗
Bioactive recombinant methionyl bovine prolactin: structure-function studies using site-specific mutagenesis.
A method has been developed for the extraction from transformed Escherichia coli cells of methionyl bovine PRL (met-bPRL) in a relatively pure form. While the extracted met-bPRL was as reactive as the native hormone with respect to polyclonal anti-bPRL antibodies, its bioactivity, as measured by the Nb2 lactogen in vitro bioassay, was relatively low. The bioactivity of the met-bPRL could be increased to the same order as that of the native hormone by treatment with a mixture of oxidized and reduced thioredoxin. A number of variant met-bPRLs containing specific amino acid changes have been generated by site-specific mutagenesis. The changes involved the substitution (or deletion) of some of the conserved amino acids in bPRL by the different amino acids present at the corresponding positions in the related, but nonlactogenic bovine GH. Nine mutants containing single amino acid changes had bio- and immunoactivities of the same order as those of met-bPRL. One mutant, which incorporated two of the single amino acid changes (serine 62 to threonine and threonine 65 to alanine), had immunoactivity approximating that of met-bPRL but much lower bioactivity (45%). A further mutant, generated by the deletion of tyrosine 28, had essentially no bioactivity although it could not be distinguished immunologically from met-bPRL or bPRL. The findings are discussed in the light of the putative three-dimensional PRL structure and current hypotheses which seek to relate specific regions of PRL to lactogenic activity. It appears that the first putative alpha-helix of bPRL is important for the binding and mitogenic activity of the hormone.
Amino Acid Sequence↗