bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of channel activation in cognitive enhancement mediated by α7 nicotinic acetylcholine receptors
Authors: Briggs Clark A , Grønlien Jens Halvard , Curzon Peter , Timmermann Daniel B , Ween Hilde , Thorin‐Hagene Kirsten , Kerr Paige , Anderson David J , Malysz John , Dyhring Tino , Olsen Gunnar M , Peters Dan , Bunnelle William H , Gopalakrishnan Murali
Published: October 2009

Background and purpose: Several agonists of the α7 nicotinic acetylcholine receptor (nAChR) have been developed for treatment of cognitive deficits. However, agonist efficacyin vivois difficult to reconcile with rapid α7 nAChR desensitizationin vitro; and furthermore, the correlation betweenin vitroreceptor efficacy andin vivobehavioural efficacy is not well delineated. The possibility that agonists of this receptor actually functionin vivoas inhibitors via desensitization has not been finally resolved.

Experimental approach: Two structurally related α7 nAChR agonists were characterized and used to assess the degree of efficacy required in a behavioural paradigm.

Key results: NS6784 activated human and rat α7 nAChR with EC50s of 0.72 and 0.88 µM, and apparent efficacies of 77 and 97% respectively. NS6740, in contrast, displayed little efficacy at α7 nAChR (<2% in oocytes, ≤8% in GH4C1 cells), although its agonist‐like properties were revealed by adding a positive allosteric modulator of α7 nAChRs or using the slowly desensitizing α7V274T receptor. In mouse inhibitory avoidance (IA) memory retention, NS6784 enhanced performance as did the 60% partial agonist A‐582941. In contrast, NS6740 did not enhance performance, but blocked effects of A‐582941.

Conclusions and implications: Collectively, these findings suggest that a degree of α7 nAChR agonist efficacy is required for behavioural effects in the IA paradigm, and that such behavioural efficacy is not due to α7 nAChR desensitization. Also, a partial agonist of very low efficacy for this receptor could be used as an inhibitor, in the absence of α7 nAChR antagonists with favourable CNS penetration.
Effect of the CB1receptor antagonists rimonabant and AM251 on the firing rate of dorsal raphe nucleus neurons in rat brain slices
Authors: Mendiguren Aitziber , Pineda Joseba
Published: October 2009

Background and purpose: Previous studies have suggested a regulation of 5‐hydroxytryptamine (5‐HT) neurons by the endocannabinoid system. The aim of our work was to examine the effect of two CB1receptor antagonists, SR141716A (rimonabant, Sanofi‐Synthélabo Recherche, Montpellier, France) and N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide (AM251, Tocris Cookson, Bristol, UK), on the firing rate of dorsal raphe nucleus (DRN) neurons.

Experimental approach: Single‐unit extracellular recordings were performed to study the effect of CB1receptor antagonists in slices of the DRN from rat brain.

Key results: Rimonabant (1 µM) and AM251 (1 µM) decreased the firing rate of about 50% of all the recorded DRN 5‐HT cells. The GABAAreceptor antagonist picrotoxin (20 µM) (Sigma) prevented and also reversed the inhibitory effect of rimonabant (1 µM) and AM251 (1 µM), suggesting that CB1receptors regulate 5‐HT neurons through the GABAergic system. However, the CB1/CB2receptor agonist R‐(+)‐[2,3‐dihydro‐5‐methyl‐3‐[(morpholinyl)‐methyl]pyrrolol[1,2,3‐de]‐1,4‐benzoxazinyl]‐(1‐naphthalenyl) methanone mesylate salt (10 µM) (WIN55212‐2, Sigma, St. Louis, MO, USA) failed to change the firing activity of non‐5‐HT (presumably GABAergic) neurons in the DRN. The endocannabinoid N‐(2‐hydroxyethyl)‐5Z,8Z,11Z,14Z‐eicosatetraenamide (anandamide, Tocris Cookson) (10 µM) also inhibited the firing activity of a number of 5‐HT neurons, but this inhibition was not blocked by rimonabant (1 µM) or AM251 (1 µM), and the stable analogue R‐(+) N‐(2‐hydroxy‐1methylethyl)‐5Z,8Z,11Z,14Z‐eicosatetraenamide (methanandamide, Tocris Cookson) (10 µM) did not mimic this effect. The selective CB1receptor agonist arachidonoyl‐2‐chloroethylamide (ACEA) (1 µM) only slightly increased the firing rate of DRN 5‐HT cells.

Conclusions and implications: These results suggest a tonic/constitutive regulation of DRN 5‐HT neurons by the endocannabinoid system, which may occur through a CB1receptor‐mediated inhibition of the GABAergic system. The inhibitory effect of anandamide may be mediated through a CB1receptor‐independent mechanism.
Effects of 7,8‐dihydro‐8‐oxo‐deoxyguanosine on antigen challenge in ovalbumin‐sensitized mice may be mediated by suppression of Rac
Authors: Ro JY , Kim DY , Lee S‐H , Park JW , Chung M‐H
Published: October 2009

Background and purpose:  Earlier we reported that 7,8‐dihydro‐8‐oxo‐deoxyguanosine (8‐oxo‐dG), an oxidatively modified guanine nucleoside, exerted anti‐inflammatory activity through inactivation of the GTP binding protein, Rac. In the present study, the effects of 8‐oxo‐dG were investigated on responses to antigen challenge in sensitized mice, as Rac is also involved at several steps of the immune process including antigen‐induced release of mediators from mast cells.

Experimental approach:  Mice were sensitized and challenged with ovalbumin without or with oral administration of 8‐oxo‐dG during the challenge. Effects of 8‐oxo‐dG were assessed by measuring lung function, cells and cytokines in broncho‐alveolar lavage fluid (BALF) and serum levels of antigen‐specific IgE. Rac activity in BALF cells was also measured.

Key results:  8‐oxo‐dG inhibited the increased airway resistance and decreased lung compliance of sensitized and challenged mice to the levels of non‐sensitized control mice and lowered the increased leukocytes particularly, eosinophils, in BALF. Furthermore, 8‐oxo‐dG suppressed allergy‐associated immune responses, such as raised anti‐ ovalbumin IgE antibody in serum, increased expression of CD40 and CD40 ligand in lung, increased interleukin‐4, ‐5, ‐13, interferon‐γ and tumour necrosis factor‐α in BALF and mRNA levels of these cytokines in BALF cells, dose‐dependently. The corresponding purine, 8‐oxo‐guanine, showed no effects in the same experiments. Finally, 8‐oxo‐dG, but not 8‐oxo‐guanine, inhibited the increased Rac activity in sensitized and challenged mice.

Conclusion and implications:  8‐Oxo‐dG had anti‐allergic actions that might be mediated by Rac inactivation. This compound merits further evaluation of its therapeutic potential in allergic asthma.
Desensitization of endothelial P2Y1 receptors by PKC‐dependent mechanisms in pressurized rat small mesenteric arteries
Authors: Rodríguez‐Rodríguez R , Yarova P , Winter P , Dora KA
Published: October 2009

Background and purpose: Extracellular nucleotides play a crucial role in the regulation of vascular tone and blood flow. Stimulation of endothelial cell P2Y1 receptors evokes concentration‐dependent full dilatation of resistance arteries. However, this GPCR can desensitize upon prolonged exposure to the agonist. Our aim was to determine the extent and nature of P2Y1 desensitization in isolated and pressurized rat small mesenteric arteries.

Experimental approach: The non‐hydrolyzable selective P2Y1 agonist ADPβS (3 µM) was perfused through the lumen of arteries pressurized to 70 mmHg. Changes in arterial diameter and endothelial cell [Ca2+]iwere obtained in the presence and absence of inhibitors of protein kinase C (PKC).

Key results: ADPβS evoked rapid dilatation to the maximum arterial diameter but faded over time to a much‐reduced plateau closer to 35% dilatation. This appeared to be due to desensitization of the P2Y1 receptor, as subsequent endothelium‐dependent dilatation to acetylcholine (1 µM) remained unaffected. Luminal treatment with the PKC inhibitors BIS‐I (1 µM) or BIS‐VIII (1 µM) tended to augment concentration‐dependent dilatation to ADPβS (0.1–3 µM) and prevented desensitization. Another PKC inhibitor, Gö 6976 (1 µM), was less effective in preventing desensitization. Measurements of endothelial cell [Ca2+]iin pressurized arteries confirmed the P2Y1 receptor but not M3muscarinic receptor desensitization.

Conclusions and implications: These data demonstrate for the first time the involvement of PKC in the desensitization of endothelial P2Y1 receptors in pressurized rat mesenteric arteries, which may have important implications in the control of blood flow by circulating nucleotides.
Adenosine A1 receptor blockage mediates theophylline‐associated seizures
Authors: Fukuda Mitsumasa , Suzuki Yuka , Hino Hitomi , Kuzume Kazuyo , Morimoto Takehiko , Ishii Eiichi
Published: October 2009

Theophylline‐associated seizures (TAS) often progress to prolonged or treatment‐resistant convulsions. Theophylline is a nonselective adenosine receptor antagonist. Adenosine is an endogenous anticonvulsant that can terminate seizures. Fever and young age have been reported to be risk factors for TAS. To elucidate the mechanism of TAS, we investigated the effect of theophylline and adenosine receptor ligands on hyperthermia‐induced seizures in juvenile rats. The treatment dose of theophylline or control saline was injected intraperitoneally 1 h before hyperthermia‐induced seizures. The seizure threshold in the theophylline group was significantly lower and seizure duration was significantly longer than those in the control group. The addition of a selective adenosine A1 receptor agonist and an adenosine kinase inhibitor completely counteracted the effects of theophylline. Moreover, a selective A1 antagonist caused a significantly longer seizure duration compared with the control. These findings suggest that blockage of the adenosine A1 receptor is the main cause of TAS.
Sequential intrarectal diazepam and intravenous levetiracetam in treating acute repetitive and prolonged seizures
Authors: Modur Pradeep N. , Milteer Warren E. , Zhang Song
Published: October 2009

In this retrospective study of institutionalized patients with mental retardation, we present the efficacy and safety of sequential treatment with intrarectal diazepam (IRD) gel (Diastat) and intravenous levetiracetam (IVL) in comparison with either treatment alone for acute repetitive or prolonged seizures (ARPS). We defined ARPS as ≥3 seizures of any type within 1 h or a single seizure of any type lasting ≥3 min. Eighty‐eight ARPS episodes were treated in 25 patients (14 female, age 21–72 years), with mainly symptomatic generalized epilepsy. There were no adverse events directly attributable to the administration of IRD or IVL. Seizure recurrence within 4 h of treatment, the primary outcome measure, was significantly lower after combined sequential IRD + IVL treatment (3 of 36) compared to IRD alone (6 of 24, p = 0.048) or IVL alone (10 of 28, p = 0.039). There was no statistically significant difference between the individual IRD and IVL treatments (p = 0.604). The estimated odds ratio (OR) indicated that the risk of seizure recurrence was higher after IRD or IVL monotherapy compared to combined IRD + IVL treatment. Subsequent emergency room (ER) transfers following seizure recurrence were least likely after IVL treatment (10%) compared to combined IRD + IVL (67%) or IRD (83%) treatment. These findings suggest that although IRD or IVL monotherapy is efficacious, the combination is superior in controlling ARPS in this special group of institutionalized patients. In addition, we speculate that a more reliable onset of action after IVL treatment results in rapid seizure control and fewer ER transfers, despite seizure recurrence.
The ketogenic diet in treatment of two adults with prolonged nonconvulsive status epilepticus
Authors: Wusthoff Courtney J. , Kranick Sarah M. , Morley James F. , Christina Bergqvist A. G.
Published: October 2009

Prolonged status epilepticus (SE) can be refractory to conventional interventions, with high rates of subsequent morbidity and mortality. A high fat, low protein, low carbohydrate ketogenic diet (KD) has been used successfully to treat intractable epilepsy. However, its possible role in prolonged SE has not been well described. We report successful use of the KD in two adult patients with prolonged nonconvulsive SE (NCSE) refractory to multiple other interventions. Our observations suggest induction of ketosis may be a novel strategy to safely and effectively treat status in adults even after weeks to months of refractory seizures. Although there are few data regarding the use of the ketogenic diet in the treatment of adult epilepsy syndromes, it may be an option for the treatment of adults with refractory, prolonged SE.
Innate but not adaptive immune responses contribute to behavioral seizures following viral infection
Authors: Kirkman Nikki J. , Libbey Jane E. , Wilcox Karen S. , White H. Steve , Fujinami Robert S.
Published: October 2009

Purpose:  To examine the role of innate immunity in a novel viral infection–induced seizure model.

Methods:  C57BL/6 mice, mouse strains deficient in interleukin (IL)‐1RI, IL‐6, tumor necrosis factor (TNF)‐RI, or myeloid differentiation primary response gene 88 (MyD88), or transgenic mice (OT‐I) were infected with Theiler’s murine encephalomyelitis virus (TMEV) or were mock infected. Mice were followed for acute seizures. Tissues were examined for neuron loss, the presence of virus (viral RNA and antigen), perivascular cuffs, macrophages/microglia, and gliosis, and mRNA expression of IL‐1, TNF‐α, and IL‐6.

Results:  IL‐1 does not play a major role in seizures, as IL‐1RI‐ and MyD88‐deficient mice displayed a comparable seizure frequency relative to controls. In contrast, TNF‐α and IL‐6 appear to be important in the development of seizures, as only 10% and 15% of TNF‐RI‐ and IL‐6‐deficient mice, respectively, showed signs of seizure activity. TNF‐α and IL‐6 mRNA levels also increased in mice with seizures. Inflammation (perivascular cuffs, macrophages/microglia, and gliosis) was greater in mice with seizures. OT‐I mice (virus persists) had a seizure rate that was comparable to controls (no viral persistence), thereby discounting a role for TMEV‐specific T cells in seizures.

Discussion:  We have implicated the innate immune response to viral infection, specifically TNF‐α and IL‐6, and concomitant inflammatory changes in the brain as contributing to the development of acute seizures. This model is a potential infection‐driven model of mesial temporal lobe epilepsy with hippocampal sclerosis.
Smith and Living Wages: Arguments in Support of a Mandated Living Wage
Authors: Clary Betsy Jane
Published: October 2009

Abstract

Adam Smith was a proponent of living wages for labor for reasons of growth and for reasons of equity. There is ample evidence in the body of Smith's work to support the thesis that Smith would support public policies that might ensure the achievement of a living wage. The argument rests, in part, on the conclusion that Smith had reservations concerning the ability of the economy to experience sufficient growth and the ability of growth, if achieved, to secure living wages. This article argues that, given Smith's views about justice and given Smith's ideas, as part of the Scottish Enlightenment, of how the rules of justice evolve, a living wage law could be one of the general rules of which Smith could approve.
Too Much Competition in Higher Education? Some Conceptual Remarks on the Excessive‐Signaling Hypothesis
Authors: Mause Karsten
Published: October 2009

Abstract

Within the economics of higher education, there is a small but influential literature that describes and analyzes the outcomes of competitive processes on markets for higher educational services. Colleges and universities in the United States currently invest a vast amount of resources in order to attract well‐qualified students. Costly activities like advertising, infrastructure investments, the recruitment of academic stars, or the granting of merit‐based tuition discounts can be interpreted as different forms of “market signaling” in the sense of Spence. According to some social science authors, these signaling activities have reached a dimension that has to be classified as excessive or socially wasteful from a welfare‐economic viewpoint. The present article makes some conceptual remarks on this excessive‐signaling hypothesis, and intends to contribute to the debate about the (potentially) harmful and beneficial effects of competition in higher education.
Physiological Basis for Transfusion Therapy in Hemorrhagic Disorders: A Critical Review
Authors: Aggeler Paul M.
Published: October 2009

The theme of this issue is the preservation of plasma clotting factors. Dr. Aggeler was invited to prepare an editorial on this subject. He became so engrossed that before he knew it his editorial had grown to the proportions of this review which is presented as an “editorial review.” (Editor)
Optimal Conditions for Storage of Fresh Frozen Plasma
Authors: Anstall Harold B. , Grove‐Rasmussen Morten , Shaw Robert S.
Published: October 2009

Small aliquots of plasma in 3.8 per cent trisodium citrate were stored at −15, −30 and −50 C. Lengthening of the recalcification time after 24 hours followed by progressive shortening for 10–14 days was observed at −15 and −50 C. At −30 C. no significant changes occurred until two months had elapsed. Assay of clotting factors VII and X, VIII and IX revealed essentially that the activity of each rose gradually over a span of 12–14 days after an initial decline at −15 C. and −50 C. At −30 C. factors VIII and IX were stable for at least two months. Factor V level declined gradually at −15 C. and −50 C. but no significant fall was observed at −30 C. The increase in the activity of factor VIII observed during storage at −15 and −50 C. was eliminated by prior adsorption with Celite which is believed to remove an activation product of Hageman factor and Plasma Thromboplastin Antecedent. There seemed to be somewhat greater instability of plasma stored in untreated glass containers than in cellulose nitrate or in siliconized glass. Storage temperatures below −40 C. and above −25 C. appear to be unfavorable for plasma coagulation factors.
The Influence of Low Temperature‐Storage on the Heparin Tolerance of Human Plasma
Authors: Anstall Harold B. , Grove‐Rasmussen Morten
Published: October 2009

Plasma stored at −50 C. or lower develops a resistance to heparin as demonstrated by progressive shortening of the thrombin time. Adsorption with Celite powder or barium sulfate before or after freezing eliminates this effect. Plasma kept at −30 C. did not develop resistance to heparin after seven days.
Second Example of Hemolytic Disease of the Newborn Caused by Anti‐Jkb
Authors: Geczy A. , Leslie M.
Published: October 2009

Mild hemolytic disease developed in the second child of a woman who gave no history of transfusions. The antibody was identified as anti‐Jkb. The antiglobulin method gave the strongest reactions but the antibody also agglutinated test cells in saline at room temperature and at 37 C. No difficulty was encountered in determining the presence of the Jkb antigen in cord blood erythrocytes.
Studies on Bank Blood Collected and Stored under Various Conditions with Particular Reference to Its Use in Open Heart Surgery
Authors: Perkins Herbert A. , Rolfs Mary R. , Acra D. J.
Published: October 2009

A few of the factors responsible for the preservation of the characteristics of fresh blood during storage have been studied, with particular reference to the provision of donor blood for open heart surgery. It has been indicated that present data leave us no reason to think that platelet viability and the level of labile clotting factors in stored blood will be any different whether the blood is collected by gravity or with the aid of vacuum. Changes in bloods stored at 4C. for a 21 day period were investigated with ACD, heparin and Edglugate‐Mg as the anticoagulants. The studies on heparinized blood suggest that after two or three days, the fall in platelets and the rise in plasma potassium and hemoglobin are so much greater than occur in ACD that storage for longer periods than that will probably never be safe. On the other hand, in vivo studies indicate that 24‐hour‐old heparinized blood is just as safe to use as four‐hour‐old blood. Edglugate‐Mg was developed in an effort to get around the limited storage period of heparinized blood. Results reported here show that plasma potassium levels rise very rapidly in this type of blood. Platelets are not well‐preserved in vitro, and Factor V levels are apparently low soon after collection.
Effect of Prednisolone on Incompatible Blood Transfusions
Authors: Hewitt Wilmer C. , Wheby Munsey , Crosby William H.
Published: October 2009

In control experiments small volumes of incompatible, chromium51 tagged red cells were given to recipients. Several days later the studies were repeated 30 minutes after the intravenous administration of prednisolone. Prednisolone was found completely ineffective in prolonging the survival of small amounts of red cells in the presence of incompatible antibodies of the ABO and Rh systems.
The Expected “Bombay” Groups OhA1 and OhA2
Authors: Aloysia Sister Mary , Gelb A. G. , Fudenberg H. , Hamper Jean , Tippett Patricia , Race R. R.
Published: October 2009

An American family of English extraction is reported in which two Oh (“Bombay”) members have transmitted A2 genes to their children thus demonstrating that the expression of the gene A2, like that of the gene B, can be suppressed in this phenotype. Another American family, of French extraction, shows with a high degree of probability that the expression of the gene A1 can be similarly suppressed.
The Phenotype Lu(a−b−) Together with Unconventional Kidd Groups in One Family
Authors: Crawford Mary N. , Greenwalt T. J. , Sasaki T. , Tippett Patricia , Sanger Ruth , Race R. R.
Published: October 2009

Minus‐minus blood group phenotypes are characterized by the absence of any detectable phenotypic representation of the alleles expected at the determining gene loci. Double minus phenotypes have been found in most blood group systems but all individuals thus far tested for the Lutheran factors have been Lu(a+b+), Lu(a+b+) or Lu(a−+). Six individuals with the hitherto undisclosed blood group Lu(a−b−) were found in three generations of a Caucasian family.

Unlike the other minus‐minus phenotypes, to which recessive genetical backgrounds have been assigned, Lu(a−b−) appears to be a dominant character.

The Kidd groups of the family are also anomalous: The proposita and her two brothers are Lu(a−b−), Jk(a+b−) yet their father is Lu(a−b−), Jk(a−b+) and their mother is Lu(a−b+), Jk(a+b−). Possible genetical backgrounds are discussed.
A Critique of the Theoretical Hazard of Inter vs. Intra‐Racial Transfusion*
Authors: Giblett Eloise R.
Published: October 2009

From the frequencies of the red cell antigens of Caucasians and American Negroes, the possibilities of antigenic exposure from inter and intra‐racial transfusion of blood were calculated. The figures obtained were then modified to take into consideration the relative potency of the individual antigens as well as the behavior of their antibodies. The results lend no support to the alleged advantage of intra‐racial over inter‐racial transfusion, since the order of magnitude of the antibody stimulation risk from all four kinds of transfusion is the same. From the standpoint of patient safety, emphasis should be placed on the performance of a sensitive compatibility test, rather than on a consideration of the racial origin of either the donor or the recipient.
Hemolytic Disease of the Newborn Apparently Caused by Anti‐Lua
Authors: Francis Betty J. , Hatcher David E.
Published: October 2009

Report of the first example of pure anti‐Lua associated with hemolytic disease of the newborn. Of special interest is the fact that this serum demonstrated a marked prozone reaction in saline, papain and indirect Coombs titrations, and is the first anti‐Lua serum to react well by the indirect Coombs technic.
Thymol Turbidity and Thymol Flocculation Tests As a Screening Technic to Detect Blood Donors Carrying the Hepatitis Virus
Authors: Alsever John B. , Barger James D.
Published: October 2009

Six‐month follow up study showed a hepatitis case rate of 1.55% in 905 patients receiving “abnormal” blood and 0.88% in 1,480 receiving nothing but “normal” blood, based on screening at the 95% confidence level of 8.0 T.T. units in clear sera and in lipemic sera of 8.0 units or more with a positive flocculation test (from studies of 52,662 consecutive donors reported in Part I). Significantly, screening at the 99% level gave less specific results: a 1.06% rate in controls and 1.42% in the test cases. The observed differences in rates are not statistically significant: twice the standard error of the difference in percentages is 0.9%, the Chi Square test showed P = 0.15 (at 95%) and 0.70 (at 99%). The donor (unit) case rates were essentially identical (0.346) in the test series and in the controls at both screening levels and the difference in hepatitis case rates was exactly proportional to the difference in the average donor exposure of the two groups at each screening level. The two groups of cases received 14% of the total blood units available and this was representative of the total available as judged by the mean T.T. values of blood received by the study cases. There was a steady increase in the hepatitis case rate from 0.6% in single unit transfusions (29% of cases) to 2.6% when four units were used, with a rate of 1.1% in those receiving five units or more (19%), suggesting the risk of hepatitis is maximal in transfusions of four or more units. Cogent reasons are presented for abandoning attempts to use nonspecific liver function tests for donor screening to eliminate significant numbers of donor carriers.
Magnetoelectrophoresisxs
Authors: Murphy William P. , Dandliker Walter B. , Keller J. Walter
Published: October 2009

The theory of magnetoelectrophoresis of erythrocytes is described and a system of red cell separation from plasma is presented in detail. The apparatus has been designed and built and tested to demonstrate its effectiveness. The steps necessary to make this process applicable to the routine donor room are described.
Actively Acquired Tolerance in Fetal‐Maternal Combinations: A Review**
Authors: Solomon Joel M. , Yokoyama Mitsuo
Published: October 2009

Two hypotheses have been developed as partial explanations of the protective mechanisms involved in Rh hemolytic disease. The first is based on the observations of Levine and others that Rh erythroblastosis is less likely to arise when the ABO blood group of the mother is serologically incompatible with that of the fetus. According to this theory, fetal blood cells are rapidly destroyed by maternal iso‐antibodies and removed from her circulation before the sensitization has sufficient time to develop. The second, due to Owen, is based on the phenomenon of actively acquired tolerance. This theory asserts that maternal blood cells may enter the fetal blood stream during the critical period in which the organism “learns” to recognize its tissues as its own. Thus, an Rh negative fetus transfusedin uterowith Rh positive cells might be expected to be tolerant of further exposures to the Rh antigen in adult life. Owen's data, based upon sensitization of the Rh negative mother show a distinct correlation with the Rh type of her mother. The available evidence is not sufficient to exclude one of the two hypotheses, and it is possible that both operate. The data for fetal‐maternal transfer of blood cells is far more conclusive than that for passage in the other direction. Definitive proof of tolerance to Rh antigens, however, requires further study.
The Providence Hospital Blood Conservation Program
Authors: McCoy Kenneth L.
Published: October 2009

In 1953, the Medical Staff adopted in its bylaws “Indications for Blood Transfusion,” which are in brief as follows: 1. To replace needed whole blood volume; 2. For oxygen transport, (A) Anemic patient, otherwise well, must have seven or less Gm. per cent of hemoglobin, (B) Anemic patient with complications affecting oxygenation or is to undergo anesthesia may be transfused if the hemoglobin is less than 10 Gm. per cent; 3. Exchange transfusion, and 4. Fresh whole blood is indicated only in rare instances of dyscrasias where a labile element is important. In the period from 1953 to 1960, the application of these indications has resulted in a decreasing “use factor” (units transfused annually divided by the number of patients) from 0.237 to 0.110. The benefits achieved are the following: Limits the transfusions to patients having valid medical indications, protects the patients from the hazards of unnecessary transfusions, and eases the burden of donor recruitment and blood collection.
Agglutinability of Red Cells After Long‐Term Storage in the Frozen State
Authors: Strumia Paul V. , Strumia Max M. , Colwell Louise S. , Torg Barbara
Published: October 2009

A description of a simple method for preservation of red cells modified by lactose‐dextrose solution in the frozen state at —93 C. The agglutinability as measured by a titration of anti‐sera vs. fresh and frozen cells was maintained after periods of storage of up to three years for the blood factors A, B, C, D, E, c, e, K, k, M, N, and Fya. S and s were also still reactive after freezing and thawing.
Preliminary Screening of Blood Donors with the Microhematocrit Test for Red Cell Volume and the Plasmacrit Test for Syphilis (HCT‐PCT Method)
Authors: Don Rita L. , Orlowski Don , Alsever John B.
Published: October 2009

The micro HCT‐PCT method and the CuSO4—VDRL method were compared in the screening of 10,598 consecutive blood donors. The more accurate micro HCT at 40 to 60 per cent limits (13.5 Gm. per cent minimum Hgb.) rejected 4 per cent of the donors as compared to 2.9 per cent with CuSO4 at the 12.5 Gm. per cent Hgb. level. Based on an earlier study comparing the CuSO4 method at the 12.5 and 13.5 Gm. per cent levels in over 7,000 donors, the rate at 13.5 Gm. per cent would have been 3.2 per cent. The reasons for the difference between the two test methods are presented. The opportunity to inspect the plasma resulted in the advance rejection of 454 donors (4.3%) for excessive chyle, six for apparent icterus, and one for abnormal buffy coat. The rate of positive serology was 2.2 per cent with the PCT test, again permitting advance rejection, as compared to a rate of 1.7 per cent with the VDRL, which is done after donation. There were nine negative PCT tests which were positive with the VDRL during a period of technical difficulties with outside diameter variation in the special PCT capillaries, eight of which were confirmed as false positive VDRL results. There were no negative PCT tests with positive VDRL results after this problem was corrected. The HCT‐PCT method of donor screening should be substituted for the CuSO4—VDRL method because it provides a better quality of donor screening through a more accurate measure of red cell normalcy and advance rejection of donors with excessive chyle, icteric plasma, abnormal buffy coat or hematocrit, as well as those with a positive serology. This advantage is greatly enhanced, since use of the method results in a savings in operating costs of over 6 per cent, through the advance rejection of donors whose blood would have been unusable.
Normal Survival of Incompatible Red Cells in the Presence of Anti‐Lua
Authors: Greendyke Robert M. , Chorpenning Frank W.
Published: October 2009

A case is reported in which incompatible Lu(a+) red cells survived normally in the presence of anti‐Lua as indicated by hemoglobin‐hematocrit determinations and by differential agglutination. This fact was later confirmed by Cr51 tagged cell studies. Sensitization apparently existed prior to transfusion although it was not detected by crossmatching at that time. The direct non‐gamma antiglobulin test became positive and a potent antibody was produced which reacted well at 37 C. and in albumin, enzyme, and antiglobulin tests. The findings in this patient are discussed in the light of previously reported cases.
Naturally Occurring Anti‐M Antibodies in One Member of Fraternal Twins
Authors: Kuhns William J.
Published: October 2009

Naturally occurring anti‐M antibodies were found in the serum of a five‐month‐old Negro twin as revealed by a discrepancy between the cell blood group and the reverse blood group. The corresponding twin did not possess this antibody.

There was no apparent cause for its presence, although it was of interest that the mother was type MN. The possibility is discussed that transfer of maternal red cells to the fetus occurred and that the M agglutinogen persisted in the infant following birth until the time that it was able to respond by forming anti‐M antibodies.
Inhibition Reactions of Fourteen “Nonspecific” Seed Extracts*
Authors: Bhatia H. M. , Boyd William C.
Published: October 2009

The paper gives the results of inhibition studies on 14 “nonspecific” lectins with simple sugars and human salivas. Five seed extracts were found to show anti‐H specificity in the sense that they were inhibited by the saliva of secretor and not by saliva of nonsecretors. These anti‐H extracts were inhibited weakly or not at all with L‐fucose and salicin and thus differed from the anti‐H lectins already known. Extracts of Vicia faba and Vicia ervilia, after inhibition with certain sugars, behaved like anti‐AB but were inhibited by salivas irrespective of the secretor status of the donor.
Blood Group Studies of Jungle Indians of the Mato Grosso
Authors: Silver Richard T. , Haber Jane M. , Kellner Aaron
Published: October 2009

Studies of the blood groups of primitive jungle Indians of Brazil revealed them all to be group O with a high incidence of genes CDe, cDE, and CDE. There was a high frequency of Fya and of P and a very low frequency of K. The Diego blood group factor was present in 5 per cent of the Indians studied. A striking and unexpected finding was evidence for a third allele in the Kidd system.
Current Status of the Vel Blood Group System
Authors: Sussman Leon N.
Published: October 2009

A review of the Vel blood group system reveals that 19 thoroughly studied examples of anti‐Vel are known and at least 50 Vel negative persons are recorded. The frequency of the Vel negative person is 0.04 per cent. All cases to date have been in Caucasians. The antigen is poorly developed in cord blood, but retains reactivity in the aged, on storage at 4 C, as well as after freezing. An associated hemolysin is usually not reactivated by addition of complement after inactivation. Bromelin technics are best. Independence from most major blood groups is established. Clinical importance is in difficult crossmatching and transfusion reactions. No hemolytic disease of newborn has been reported (three examples of anti‐Vel present during pregnancy). Family studies are essential to discover compatible donors, since 25 per cent of the siblings of Vel negative persons must also be Vel negative. The American Association of Blood Banks Central File has a list of available donors. Awareness of the existence of anti‐Vel facilitates the transfusing of a patient with high frequency antibody.
The Relation of Human and Cattle Blood Groups
Authors: Stone W. H.
Published: October 2009

The blood groups of humans and of cattle are very similar, even though cattle cells are typed by a hemolytic test and human cells by an agglutination test. In each species, over 50 antigenic factors are detectable and nine to ten genetically independent systems are known. The J substance of cattle and the A substance of humans are serologically and chemically related. Both occur on the erythrocytes and in body fluids and their respective naturally occurring antibodies show seasonal variation in titer. The B system of cattle contains over 200 phenogroups detected with one or more of 20‐odd reagents; the Rh system of humans also contains over 200 phenogroups detected with ten to 12 standard reagents. As knowledge of the Rh system evolves, it more nearly parallels the B system of cattle. Hemolytic disease does not occur in cattle either naturally or by active or passive immunization. Erythrocyte chimerism is much more frequent in cattle than in humans, but sterility of females born co‐twin to males has been observed in cattle only. The excess of MN heterozygotes from intercross matings in humans has its parallel in the excess of Z heterozygotes in cattle, both phenomena are presumably associated with a heterotic effect.
Transfusion of Buffy Coat‐Poor Red Cell Suspensions Prepared by Dextran Sedimentation: Description of Newly Designed Equipment and Evaluation of Its Use
Authors: Cassell Mona , Phillips Dorothy R. , Chaplin Hugh
Published: October 2009

Modified equipment is described for use in preparation of buffy coat‐poor red cell suspensions by the dextran sedimentation procedure. The chief advantages over previously available equipment are: (a) Minimized contamination hazard, (b) Administration of the final red cell suspension from the original blood container, thereby assuring maintenance of correct donor identification. Experience with the modified equipment in preparation of 70 units of buffy coat‐poor red cells for transfusion is described. Experience with transfusion of 297 units of buffy coat‐poor red cell suspensions at Barnes Hospital during the past five years is briefly reviewed.
The Rho Variant — Du
Authors: Sturgeon Phillip
Published: October 2009

In a survey of 18,365 bloods for the incidence of the Du factor, in a population comprised approximately of 72 per cent Caucasoids, 15 per cent Negroids, 10 per cent Mexicans and 3 per cent Orientals, 78 Du bloods were found of which seven were type ccDuee. Of the latter, five came from Negroids and two from Caucasoids; the frequency among the two populations approximates respectively one in 6,000 and one in 500. In the general population of this region it is one in 2,500.

The degree of reactivity of the type ccDuee found in this study was that of the “low grade” variety. However, from the remaining 71 “low grade” Du bloods, substantially weaker examples were found among type CcDuee and ccDuEe. The indirect antiglobulin and ficinized cell method readily detected type ccDuee; however, among the weaker variants, the antiglobulin method gave the more consistent results.

It is concluded, therefore, that type ccDuee does occur in this area with a frequency that is considered significant and that its detection rests on the antiglobulin or other equally sensitive methods.
Differences in the Effect of Lactic Acid and Neutral Lactate on Glycolysis and Nucleotide Pattern in Incubated Whole Human Blood
Authors: Bishop Charles
Published: October 2009

Whole human blood collected in heparin and glucose was incubated for up to 48 hours. Glycolysis proceeded, giving rise to lactic acid formation, and in consequence the pH decreased continuously. Blood ATP levels also decreased as glycolysis slowed since glycolysis is the only energy source in the red cells of whole human blood. The decrease in glycolytic rate was shown to be entirely dependent upon the increasing acidity and not on the lactate per se, since added neutral lactate had no effect on the rate of glycolyis or the ATP level whereas added lactic acid had a profound effect on both glycolysis and ATP level.
A Simple and Practical Method for Concentrating Blood Group Antibodies
Authors: Giblett Eloise R. , Brooks Lucy E.
Published: October 2009

Concentration of serum proteins, including blood group antibodies and complement components, is achieved rapidly and economically by dialysing the serum against dry Carbowax 20‐M, a polyethylene glycol polymer with a molecular weight of 20,000. Such concentrates require no fluid or electrolyte readjustment for red cell testing and may be used for the identification of weak antibodies, the conversion of rare but unreliable antisera into useful laboratory reagents, and the preparation of serum specimens with high complement activity.
The Occasional Fallibility of in Vitro Compatibility Tests
Authors: Chaplin Hugh , Cassell Mona
Published: October 2009

A patient is described in whom rapid destruction of transfused red cells occurred repeatedly despite entirely compatible cross‐match results by a wide variety of dependable laboratory procedures. The report includes detailed serologic investigations of these phenomena, as well as the results of 17 measurements of in vivo red cell survival. A striking clinical observation was the regular onset of typical sickle cell “crisis” coincident with the rapid destruction of large volumes of donor erythrocytes.

The occasional fallibility of compatibility tests is emphasized.
Standards for Rejection of Blood Donors: A Comparison of CuSO4 Specific Gravity, Microhematocrit and Electronic Hematocrit Values with Hemoglobin Values by the Cyanmethemoglobin Technic
Authors: Perkins Herbert A. , Torg Barbara
Published: October 2009

The following tests were performed simultaneously on finger puncture blood from 200 blood donors: specific gravity by the copper sulfate screening technic, hemoglobin by the cyanmethemoglobin method, and hematocrit by the microhematocrit and also by a new electronic device.

The electronic hematocrit provides a simple and rapid technic for estimating the hematocrit, and correlated well with the microhematocrit. Neither technic correlated as closely with cyanmethemoglobin values as did the copper sulfate test. Since current standards for blood donor acceptance are based on hemoglobin levels (and in view of its simplicity), the copper sulfate technic remains the method of choice for screening donors. This can be supplemented in borderline cases by a cyanmethemoglobin determination. The electronic hematocrit could be a useful device to supplement the copper sulfate test in situations where accurate hemoglobin determinations are not available.
Blood Groups, Serum Genetic Factors and Hemoglobins in Western Solomon Islanders
Authors: Douglas R. , Jacobs J. , Hoult G. E. , Staveley J. M.
Published: October 2009

A sample of 186 Western Solomon Islanders characterizes this population by an absence of A2, high N, S associated only with N, an Le(a−b−) frequency as high as Maoris, high Rh1, and an absence of Dia, Jsa and Lua.

The high frequency of absent haptoglobins is probably related to the high malaria rate in the area. The absence of abnormal hemoglobins is noted in relation to the same disease.
The Salvage of Heparinized Blood with Acid‐Citrate‐Dextrose
Authors: Button Lawrence N. , Gibson John G. , Kevy Sherwin V.
Published: October 2009

Heparinized blood not used at operation may be salvaged by transfer to Acid‐Citrate‐Dextrose (ACD) within 24 hours after collection. Collection and transfer must be done in a closed system and adequate refrigeration maintained from collection to transfusion. In five experiments, post‐transfusion survival studies have shown the percentage of viable cells to fall to 70 per cent in about 12 days. Plasma pH, hemoglobin, and potassium levels were within the same range as those of ACD bloods stored for similar periods. Of 180 heparinized bloods not used because of changes in operative schedules, 158 were salvaged and transfused, within this limit, in other cases.
A Statistical Approach to Ordering and Usage Policies for a Hospital Blood Bank*
Authors: Elston R. C. , Pickrel Jerry C.
Published: October 2009

An electronic computer (UNIVAC 1105) is used in a simulation study to determine ordering and usage policies for a hospital blood bank. It is assumed that only type specific transfusions are given, and all use of fresh blood obtained for specific cases is excluded. A ratio of 25:4 is taken as the ratio of the cost whenever the bank is “short” of a unit for actual transfusion to the cost of an outdated unit.

Optimal inventory levels are determined for a particular bank when the oldest blood is used first and the random volunteer donor input is maintained at current levels, when this input is doubled, and when the entire input is composed of ordered blood having life of 15 days. If the random input is doubled the losses are almost quadrupled. The losses would be least if the input were completely ordered and the life of the ordered blood were not restricted; but when the ordered blood has a life of only 15 days the losses are somewhat higher than when the random input remains unchanged. Consequences of always using the freshest blood first are also examined. This policy does not appear to be feasible unless the bank contains an excessive amount of blood.
Comparison of Fetal and Adult ABH Antigens by the Quantitative Hemagglutination Technic
Authors: Solomon Joel M.
Published: October 2009

The quantitative hemagglutination technic has been used to demonstrate quantitative and qualitative differences between fetal and adult ABH antigens. Fetal antigens are, on the average, less reactive than comparable adult antigens and show significant alterations in antigenic specificity.

Fetal A1 could not be definitely distinguished from fetal A2. Qualitative variations were observed among fetal and adult H antigens detected with extracts of the seeds of Ulex europeus.

In general the quantitative reciprocity of A and H observed with adult erythrocytes is equally applicable to fetal bloods.
Pyrogens from an Historical Viewpoint*
Authors: Seibert Florence B.
Published: October 2009

In 1920 fevers that followed intravenous transfusions posed difficult problems for the surgeon, and the use of triple‐distilled water for the preparation of such solutions was recommended on an empirical basis.

A careful study of this problem led to the following conclusions: (1) that non‐pyrogenic distilled water could be dependably prepared by a single distillation in an all‐pyrex apparatus containing an adequate spray‐catching baffle; (2) that, if such water were sterilized immediately, it would remain non‐pyrogenic; (3) that non‐pyrogenic salt solutions and various other solutions for use in intravenous therapy could be made by using such water; and (4) that certain bacteria falling into the water released heat‐stable and filterable products which were responsible for the fevers; and (5) that protein products could also be prepared which would elicit no fevers on intravenous injection, if bacterial contamination was prevented during their preparation.

Pyrogen preparations were later made from Pseudomonas and certain other bacteria for use as standards. They were found to be mainly polysaccharide in nature. They caused immediate leukopenia and delayed leukocytosis and also developed tolerance to themselves on repeated injection.

Pyrogens of endogenous origin, possibly released from leukocytes, have also been found.
A Second Example of the Antibody Anti‐Jsb of the Sutter Blood Group System
Authors: Huestis Douglas W. , Busch Shirley , Hanson Mary Lu , Gurney Clifford W.
Published: October 2009

An antibody defined as anti‐Jsb of the Sutter blood group system was discovered in the serum of a much transfused Chicago Negro woman of group B, Rho (cDue), Js (a+b–). Antibodies to rh′ (C) and rh″ (E) were also present. Tests with 460 Chicago Negro donors, all rh′ (C)‐negative and rh″ (E)‐negative, revealed three cases of phenotype Js (a+b–), an incidence of 0.65 per cent.
Damage to Red Cells Due to Their Collection and Storage in ACD
Authors: Bishop Charles
Published: October 2009

Experiments were performed using aliquots of the same blood incubated at 37 C. in spinner flasks under 95%N2 – 5% CO2. Various anticoagulant systems and pH's were compared, using the rate of glycolysis and ATP levels as criteria of metabolic activity. Citrate and lower pH's were detrimental to glycolysis and the maintenance of red cell ATP levels. Non‐citrate systems that were closer to normal blood pH were superior to ACD, by the criteria used in this in vitro study. The addition of phosphate, as in the citrate‐phosphate‐dextrose system, appeared beneficial.