'Definite and material'. Coronary thrombosis and cardiologists in the 1920s.
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Angina Pectoris↗
Biomedical subjects
C Lawrence
Publications and source records attributed to C Lawrence.
Elliptocytosis associated with an abnormal alpha glycophorin.
A case of elliptocytosis associated with an undescribed abnormal alpha glycophorin (alpha GP) is reported. Using immunoblotting techniques, a clear-cut minor band 6' was detected emerging just behind the monomer of delta GP (band 6) when probed with anti-alpha GP antiserum. It also reacted with anti-peptide C antiserum, suggesting that this new band with a molecular weight of 24 K is related to the structural alteration of alpha GP and not delta GP. The erythrocyte membrane proteins of the patient exhibited a quite normal pattern, with a normal alpha spectrin/beta spectrin ratio, but the reaction with anti-protein 4.1 serum confirmed the increase in proteolytic susceptibility of her protein 4.1. The results of DNA mapping implied that the abnormality may be due to a short deletion of the heterozygote. The significance of deviation involving the alpha GP and protein 4.1 to the elliptocytic change of erythrocyte shape is briefly discussed.
Aged↗
Quantitative PCR with internal controls.
We examine the use of internal controls for estimating the expected initial copy number of the target in a polymerase chain reaction (PCR). We base our investigation on an extended branching-process model. In terms of that model, we delineate the necessary assumptions for this methodology to yield approximately unbiased answers, and we provide means for testing some of those assumptions. We show how to design a series of PCRs to attain optimal precision of the estimate. We provide an algorithm for conducting the statistical analysis of the data, including a formula for a confidence interval for the unknown expected initial copy number.
Algorithms↗
Hematologic changes in massive burn injury.
OBJECTIVE: To study and report the striking hematologic changes that occur in patients with massive burn injury. DESIGN: Case reports and description of hematologic studies. SETTING: A municipal general hospital burn unit. PATIENTS: Three severely burned patients who survived, respectively, 45 mins, 22 hrs, and 57 hrs after hospitalization. METHODS: Routine clinical hematologic laboratory studies. RESULTS: The patients had intravascular hemolysis, and their RBCs exhibited spherocytosis, fragmentation, and vesiculation. Numerous fragments of red cell membranes were originally present in the blood and cleared within 4 hrs. These fragments may have contributed to the renal failure seen in these patients. The patients also had marked pseudothrombocytosis, presumably owing to "incorrect recognition" by the automatic counter of red cell microvesicles as platelets. CONCLUSIONS: Pseudothrombocytosis should be anticipated with massive burn injury. Despite high or normal platelet counts reported by the laboratory, evidence of intravascular coagulation should be promptly investigated.
Acute Disease↗
The effect of indomethacin on anthralin inflammation.
The effect of prostaglandin inhibition, using topical indomethacin, on anthralin inflammation was studied. Indomethacin gel and gel base were applied to opposite flexor forearm skin sites of 11 volunteers for 2 h and then washed off. Anthralin and UVB were then applied to the gel-treated skin and the anthralin- and UVB-induced erythema and oedema were measured at 2, 6, 24 and 48 h using Harpenden callipers and a reflectance erythrometer. Prostaglandin inhibition was demonstrated by a significant reduction of UVB erythema at the indomethacin-treated sites compared to the gel-base-treated sites. There was a small but significant reduction in anthralin erythema, but not oedema, at the indomethacin-treated sites compared to the gel-base sites. This study demonstrates that prostaglandins, and other inflammatory mediators because the inhibitory effect was small, are involved in anthralin inflammation.
Administration, Topical↗
Teenagers and the risks of sexually transmitted diseases: a need for the provision of balanced information.
OBJECTIVE: Evaluation of teenagers' knowledge and understanding about sexually transmitted disease, conception and contraception. DESIGN: A questionnaire study. SETTING: Schools SUBJECTS: 1025 teenagers aged 15/16 years (mean 16.00). MAIN OUTCOME MEASURES: Scores attained in response to questions about sexually transmitted disease related to the sources of information given as most helpful. RESULTS: Teenagers have an incorrect understanding of the risks of sexually transmitted diseases. CONCLUSIONS: Teenagers may substantially underestimate their personal risk of contracting sexually transmitted diseases following the promotion of information about HIV/AIDS. Apparently simple messages about HIV and AIDS given in mass media advertising programmes may have unwanted results and need to be balanced by appropriate professional interpretation to teenagers.
Adolescent↗
The meaning of histories. Essay review.
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History, 18th Century↗
The unique red cell heterogeneity of SC disease: crystal formation, dense reticulocytes, and unusual morphology.
Knowledge concerning SS (homozygous for the beta s gene) red blood cell (RBC) heterogeneity has been useful for understanding the pathophysiology of sickle cell anemia. No equivalent information exists for RBCs of the compound heterozygote for the beta s and beta c genes (SC) RBCs. These RBCs are known to be denser than most cells in normal blood and even most cells in SS blood (Fabry et al, J Clin Invest 70:1284, 1981). We have analyzed the characteristics of SC RBC heterogeneity and find that: (1) SC cells exhibit unusual morphologic features, particularly the tendency for membrane "folding" (multifolded, unifolded, and triangular shapes are all common); (2) SC RBCs containing crystals and some containing round hemoglobin (Hb) aggregates (billiard-ball cells) are detectable in circulating SC blood; (3) in contrast to normal reticulocytes, which are found mainly in a low-density RBC fraction, SC reticulocytes are found in the densest SC RBC fraction; and (4) both deoxygenation and replacement of extracellular Cl- by NO3- (both inhibitors of K:Cl cotransport) led to moderate depopulation of the dense fraction and a dramatic shift of the reticulocytes to lower density fractions. We conclude that the RBC heterogeneity of SC disease is very different from that of SS disease. The major contributions of properties introduced by HbC are "folded" RBCs, intracellular crystal formation in circulating SC cells, and apparently a very active K:Cl cotransporter that leads to unusually dense reticulocytes.
Anemia, Sickle Cell↗
A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules.
Kallmann's syndrome (clinically characterized by hypogonadotropic hypogonadism and inability to smell) is caused by a defect in the migration of olfactory neurons, and neurons producing hypothalamic gonadotropin-releasing hormone. A gene has now been isolated from the critical region on Xp22.3 to which the syndrome locus has been assigned: this gene escapes X inactivation, has a homologue on the Y chromosome, and shows an unusual pattern of conservation across species. The predicted protein has significant similarities with proteins involved in neural cell adhesion and axonal pathfinding, as well as with protein kinases and phosphatases, which suggests that this gene could have a specific role in neuronal migration.
Base Sequence↗
Characterization of a murine gene expressed from the inactive X chromosome.
In mammals, equal dosage of gene products encoded by the X chromosome in male and female cells is achieved by X inactivation. Although X-chromosome inactivation represents the most extensive example known of long range cis gene regulation, the mechanism by which thousands of genes on only one of a pair of identical chromosomes are turned off is poorly understood. We have recently identified a human gene (XIST) exclusively expressed from the inactive X chromosome. Here we report the isolation and characterization of its murine homologue (Xist) which localizes to the mouse X inactivation centre region and is the first murine gene found to be expressed from the inactive X chromosome. Nucleotide sequence analysis indicates that Xist may be associated with a protein product. The similar map positions and expression patterns for Xist in mouse and man suggest that this gene may have a role in X inactivation.
Amino Acid Sequence↗
Metastatic tumor: the complementary role of the marrow aspirate and biopsy.
To determine whether bone marrow aspiration or biopsy is more sensitive in the detection of nonhematologic metastatic involvement of marrow, all 1569 consecutive paired biopsy and aspirate samples obtained between January 1975 and January 1, 1986 in an 800 bed municipal hospital were reviewed. At least eight aspirate slides and 10 biopsy cross sections were examined for each pair. In 39 samples, both biopsy and aspirate identified metastatic tumor. No biopsies contained tumor that was not also seen on the aspirate. However, five aspirate slides contained metastatic malignancies not identified on biopsy. The hematologist or oncologist viewing individual cells in a monolayer at 1000 x magnification has the advantage of identifying very small clusters of tumor cells. That accounted for three of the five positive aspirate samples in which the biopsies were negative. The other two positive aspirate slides each contained tumor on only one of eight slides. The results of our study indicate that when carefully reviewed, the aspirate is at least as sensitive as the marrow biopsy for identifying metastatic tumor. Our results indicate that marrow aspirates and biopsies are useful and complementary examinations for identifying metastatic malignancy.
Biopsy↗
Low to moderate maternal alcohol use before and during pregnancy, and neurobehavioural outcome in the newborn infant.
Of 2002 randomly selected pregnant women recruited prospectively over a three-year period for an extensive questionnaire survey, a stratified subsample of 665 mothers was selected for mother-infant follow-up on the basis of pre-pregnancy alcohol intake. Infant outcome was assessed by detailed clinical examination and application of a modified Einstein Neonatal Behavioural Assessment Schedule (ENBAS) performed at 24 to 72 hours of age. Of the infant responses to 25 ENBAS items, only tonus showed a small but significant relationship to pre-pregnancy maternal alcohol intake. The authors conclude that low to moderate maternal alcohol intake has no significant effect on newborn neurological status.
Alcohol Drinking↗
The distinct pathobiology of sickle cell-hemoglobin C disease. Therapeutic implications.
The data available clearly establish that the hyperconcentration of hemoglobin C and S inside SC cells is the main and driving mechanism for the pathologic behavior of these cells. It facilitates the polymerization of Hb S, but it also favors the tendency of Hb C to induce the formation of crystals and aggregates, abnormal morphologic shapes, and abnormally dense reticulocytes, through a particularly active K:Cl cotransport. Why these cells are endowed with a particularly active K:Cl cotransport is still a mystery; it is disproportionate with the extent of the hemolysis and the number of young cells. Is there an abnormal interaction between Hb C and the K:Cl cotransport protein in the inner aspect of the membrane? Are there abnormal interactions between Hb C and the other transport mechanisms that balance the shrinking capacity of K:Cl cotransport (as Na/H exchange)? Only future work will tell. In any case, SC disease is unique among the hemoglobinopathies in that a single intervention could correct all abnormalities: the restitution of the normal MCHC, as proven experimentally by Fabry et al. Hence, effort should be centered on looking for compounds that increase red cell volume, because in SC cells, increases in volume will not distort the cell, but restore it to the normal red cell volume and the normal red cell shape. This luxury is not available for cells with normal MCHC (the majority of the red cells in SS blood), because increasing their volume will progressively turn them into spheres, a rheologically disadvantaged shape.
Animals↗
Membrane channel protein abnormalities and autoantibodies in neurological disease.
Immunological analogues of band 3, the anion transporter of the human erythrocyte, have been identified in all cells, including both isolated neurons and neurons of the central nervous system. We hypothesized that the anion channel is altered in neurological disease associated with choreiform movements because gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in mammalian brain, binds to its receptor and opens an integral membrane chloride channel. In order to examine this hypothesis, we studied a family with a serious, progressive, genetic neurologic disorder with acanthocytosis (choreoacanthocytosis) that resembles Huntington's chorea. We selected choreoacanthocytosis because erythrocytes, which are readily obtained, are affected in this disease as well as the central nervous system. Biochemical studies of erythrocytes from the proposita, mother, and brother revealed that sulfate transport Vmax was increased, and glucose efflux was decreased. Erythrocytes exhibited immunological changes indicative of cellular aging/transporter damage. In addition, transporter reactive antibodies were present. This is the first evidence for abnormalities of membrane transport in this neurologic disorder.
Acanthocytes↗
Clinical utility of serum tests for iron deficiency in hospitalized patients.
Serum iron and ferritin measurements lack the requisite sensitivity and/or specificity to accurately diagnose iron deficiency. To determine their utility in hospitalized patients, the authors compared the results of these tests with the presence of stainable iron in bone marrow aspirates of 301 patients. Forty (13.3%) had absent marrow iron. The serum diagnosis of iron deficiency was accepted on the basis of the following: iron less than 11 mumol/L, total iron-binding capacity (TIBC) greater than 45 mumol/L, transferrin saturation (%Sat) less than 0.20, and ferritin less than 13 micrograms/L for females and less than 25 micrograms/L for males. Using these criteria, iron deficiency was correctly diagnosed by serum iron in 41%, TIBC in 84%, %Sat in 50%, and ferritin in 90% of the patients. The serum ferritin is clearly the only useful serum test for diagnosing iron deficiency in hospitalized patients but is limited by a low sensitivity. The bone marrow examination is the most sensitive test for diagnosing iron deficiency in hospitalized patients.
Anemia, Hypochromic↗
Effect of gender in centrally induced angiotensin II hypertension in dogs.
This study was designed to investigate the relation between gender, an endogenous inhibitor of the Na+-K+ pump, and volume-dependent hypertension induced by stimulation of the brain renin-angiotensin system and increased salt intake. Angiotensin II (20 ng/min i.c.v.) was infused for 4 weeks in five dogs of each sex with saline as the drinking fluid. In male dogs, angiotensin II induced parallel pressor (30%) and dipsogenic responses (70%), whereas no hypertension and no increase in fluid intake were observed in females. In contrast, the activity of the Na+-K+ pump as assessed by 86Rb uptake was independent of gender. Our data provide novel evidence that gender plays a determining role in the physiological properties of centrally administered angiotensin II.
Angiotensin II↗
Reduction of post-traumatic swelling and compartment pressure by impulse compression of the foot.
Following the discovery of a powerful venous pump in the foot that is activated by weight-bearing independently of muscular action, a pneumatic impulse device was developed to actuate this pump artificially. In a multicentre international trial the device was shown to reduce post-traumatic and postoperative swelling; pain also was alleviated. Evidence is also presented that dangerously high compartment pressures may be reduced to acceptable levels and fasciotomy avoided. We present an explanation of the clinical effects of activation of the venous footpump, based on recent improved understanding of the physiology of the microcirculation. The hyperaemic response that follows the liberation of endothelial-derived relaxing factor (EDRF) by sudden changes of pressure after weight-bearing or impulse compression is particularly important.
Adolescent↗
Membrane protein band 3 alteration associated with neurologic disease and tissue-reactive antibodies.
Immunological analogues of band 3, the anion transporter, have been identified in all cells that have been studied, including both isolated neurons and neurons of the central nervous system. We studied band 3 structural/functional relationships in a family in which the proposita has a serious, progressive, genetic neurologic disorder with acanthocytosis (choreoacanthocytosis). Biochemical studies of erythrocytes from the proposita, her mother and brother revealed that maximal sulfate transport velocity (Vmax) and sodium transport were increased, glucose efflux was decreased. Ankyrin binding was normal. Immunologic studies revealed increased IgG binding to middle-aged cells of the proposita and her brother, binding of antibodies to aged band 3 to a distinct region of band 3 in erythrocyte membranes in immunoblots, and binding of choreoacanthocytosis sera IgG to erythroid and brain band 3 and synthetic peptides of band 3 in immunoblots. Antibodies to neural and, to a lesser extent, renal tissue were observed in choreoacanthocytosis sera. These antibodies appear to have a band 3 specificity. Monoclonal antibodies to 150 residues of the carboxyl terminus of band 3 stained two band 3 fragments in immunoblots of chymotrypsin-digested membranes that are not present in control cells. This suggests that band 3 is altered in this autosomal recessive neurologic disorder. In addition, these monoclonal antibodies stained five band 3 breakdown products in membranes of untreated red cells in both control and choreoacanthocytosis cells. The possibility that a disturbance of some function of band 3 may contribute to the neurologic abnormalities in affected individuals is intriguing. This is the first evidence for abnormalities of membrane transport in the neurologic disorder known as choreoacanthocytosis.
Acanthocytes↗