BIOCHEMISTRY IN ANAESTHESIA Modern Trends In Anaesthesia. II. Aspects of Hydrogen lon Regulation and Biochemistry in Anaesthesia. Edited by Prankis T. Evans, M.B., B.S., F.R.C.S., F.F.A. R.C.S., and T. Cecil Gray, M.D., FF.A. R.C.S., Hon.F.F.A. R.A.C.S. (Pp. 219+vii; illustrated. 60s.) London: Butterworths. 1962. In this stimulating book a group of experts have written on hydrogen-ion regulation and biochemistry in anaesthesia. This vast subject has been divided rather artificially and only certain aspects of biochemistry have been covered, and the divisions are more related to clinical practice than basic physiology and biochemistry. TIhe sections have been written by specialists in each field; the material they contain is beyond criticism, and there is valuable practical advice. Some chapters are well written, though others are not so easy to read. All are packed with information, and, what is equally valuable, they provide a source of further information for the inquiring mind, for the references and bibliographies are excellent. It is a pleasure to have complicated electrophysics presented in a readable way (\" Measurement of pH and Pco l\"); \"The Cholinesterases\" is an embracing account of difficult physiological and biochemical problems. Throughout the book there is a wealth of valuable material, indeed so much so that at times too much appears to have been attempted within the space available, as in \" Effects of Hypercapnia.\" These are minor criticisms of a good book, or perhaps it would be wiser to call it a collection of papers on chosen subjects, for there is understandably a lack of cohesion among the various chapters, and even some slight overlapping, which renders the whole less valuable than its several parts. No one can read these papers without interest and profit (and occasionally amusement) and they should fulfil the editor's hope that they will stimulate further interest in basic science. The book is well presented; the printing and paper are good, but the price will not encourage widespread use of the book among the younger members of our specialty. G. E. H. ENDEPBY.

Blood Groups in Man.

The ability to taste the substance phenylthiocarbamide (PTC) has been widely used for genetic and anthropological studies, but genetic studies have produced conflicting results and demonstrated complex inheritance for this trait. We have identified a small region on chromosome 7q that shows strong linkage disequilibrium between single-nucleotide polymorphism (SNP) markers and PTC taste sensitivity in unrelated subjects. This region contains a single gene that encodes a member of the TAS2R bitter taste receptor family. We identified three coding SNPs giving rise to five haplotypes in this gene worldwide. These haplotypes completely explain the bimodal distribution of PTC taste sensitivity, thus accounting for the inheritance of the classically defined taste insensitivity and for 55 to 85% of the variance in PTC sensitivity. Distinct phenotypes were associated with specific haplotypes, which demonstrates that this gene has a direct influence on PTC taste sensitivity and that sequence variants at different sites interact with each other within the encoded gene product.

https://science.sciencemag.org/content/sci/299/5610/1221.full.pdf

Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide

Like physicists striving to develop a unified field theory, immunologists are attempting to bring order to the microcosmos of defense reactions. Indications are that one of the most important constants in this microcosmos is the major histocompatibility complex (MHC) of the species. A test of any interpretation of the MHC's role in immunity is how well it explains this system's polymorphism. One of the most crucial questions an MHC hypothesis must answer is: Why are there so many alleles at this complex?

https://science.sciencemag.org/content/sci/203/4380/516.full.pdf

The major histocompatibility complex of the mouse.

Publisher Summary This chapter presents the proteins of the alternative pathway and their special properties as enzymes, enzyme substrates, and regulators. The participation with the classical pathway components, C5–C9, in membrane attack is considered. The surprising discovery of the activation of the alternative pathway by many systems other than antibody is emphasized along with the key role played by C3 and its component parts. The alternative pathway of complement activation is closely linked to natural resistance to infections. The chapter discusses biological manifestations of alternative pathway activation. This area of research has been facilitated by isolated cytolytic alternative pathway that includes the five proteins of the membrane attack pathway. Thus, antibody-independent killing by the cytolytic pathway of bacterial and animal cells, including virus-infected human cells, is illuminated. The biomedical relevance of the alternative pathway as part of the complement system is unquestionable. Once activated, it can mark particles for phagocytosis, induce killing of nucleated cells or of bacteria, and cause lysis of enveloped viruses or virus-infected cells. It generates biologically active protein fragments, such as Bb, C3a, C3b, and C5a that influence function and behavior of inflammatory cells and cells of the immune system.

Molecular biology and chemistry of the alternative pathway of complement.

The chromosomal distribution of alleles for HLA-A,-B,-C, and -DR and the serum complement protein alleles of factor B and C2 and C4 was studied in normal Caucasian families. Eight combinations of HLA-B, DR, BF, C2, C4A, and C4B markers were found to occur in haplotypes at frequencies significantly higher than expected. In these combinations, which were defined as extended major histocompatibility complex haplotypes, HLA-A showed limited variation. A possible mechanism for the maintenance of extended haplotypes are human analogs of murine t mutants which are characterized by crossover suppression and male transmission bias. One human 6p haplotype, HLA-B8, DR3, SCO1, GLO 2, was found to be transmitted from males to 83% of their offspring. The same haplotype with GLO 1 had no transmission bias. It is suggested that this GLO 2-marked chromosome is a human analog of a murine t mutant.

http://www.pnas.org/content/80/1/259.full.pdf

Extended HLA/complement allele haplotypes: evidence for T/t-like complex in man.

. The HL-A histocompatibility locus is closely linked to that for the glycinerich β-glycoprotein polymorphism. No recombinants were seen among 44 children from 12 informative families.

Linkage of HL-A and GBG.

The separation of lymphocytes from the other blood cells is based on the differences in their specific gravity. Centrifugation of whole blood against an isopaque-ficoll gradient results in the formation of three separate layers: the top one contains the slowly sedimenting cells (lymphocytes, platelets and some monocytes); the inter­ mediate one, the granulocytes; the bottom layer contains the erythrocytes, aggregated by the ficoll.

Micromethod for Rapid Separation of Lymphocytes from Peripheral Blood

Fifteen antigenic determinants are known to be related to the Kell blood group. Some boys with X-linked chronic granulomatous disease have the very rare McLeod or Ko phenotype on their red cells. Serological studies of the McLeod type suggest that the weak Kell antigens that are present differ qualitatively and quantitatively from those on red cells of common Kell type. A new antigen, Kx, has been characterized and shown to be present on red cells and neutrophil leucocytes. Lack of red-cell Kx is associated with the McLeod phenotype, lack of leucocyte Kx is associated with chronic granulomatous disease.

Chronic granulomatous disease and the Kell blood groups

Summary. Human milk has been found to contain a high concentration of water-soluble I blood-group substance. Tests with 24 different anti-I sera showed that to a variable extent all of them could be inhibited by milk and some could be inhibited by strong I secretor saliva. The susceptibility of I antibodies to inhibition was not related to titer, and the results suggest that qualitative differences in the antibody-antigen reaction are responsible.

Inhibition of anti-I sera by human milk.

D. J . Anstee, G. W. G. Bird E. Brodheim, J.-P. Cartron W. Dahr, C. P. Engelfriet P. D. Issitt, J . Jgrgensen L. Kornstad, M . Lewis C. Levene, A . Lubenko D. Mallory, P. Morel R . Nordhagen, Y. Okubo M . Reid, Ph. Rouger Ch. Salmon, S. Seidl, I? Sistonen S. Wendel, G. Woodfield 7: Zelinski International Society of Blood Transfusion Socihte lnternationale de Transfusion Sanguine Section Editor: B. Habibi, Paris

F. H. Allen

Papers

Linkage of HL-A and GBG.

Micromethod for Rapid Separation of Lymphocytes from Peripheral Blood

Chronic granulomatous disease and the Kell blood groups

Inhibition of anti-I sera by human milk.

ISBT Working Party on Terminology for Red Cell Surface Antigens