bluuebunny/crossref_metadata_2025 huggingface dataset:
Starch grains on human teeth reveal early broad crop diet in northern Peru
Authors: Piperno Dolores R. , Dillehay Tom D.
Published: December 2008

Previous research indicates that the Ñanchoc Valley in northern Peru was an important locus of early and middle Holocene human settlement, and that between 9200 and 5500
14
C yr B.P. the valley inhabitants adopted major crop plants such as squash (
Cucurbita moschata
), peanuts (
Arachis
sp.), and cotton (
Gossypium barbadense
). We report here an examination of starch grains preserved in the calculus of human teeth from these sites that provides direct evidence for the early consumption of cultivated squash and peanuts along with two other major food plants not previously detected. Starch from the seeds of
Phaseolus
and
Inga feuillei
, the flesh of
Cucurbita moschata
fruits, and the nuts of
Arachis
was routinely present on numerous teeth that date to between 8210 and 6970
14
C yr B.P. Early plant diets appear to have been diverse and stable through time and were rich in cultivated foods typical of later Andean agriculture. Our data provide early archaeological evidence for
Phaseolus
beans and
I. feuillei
, an important tree crop, and indicate that effective food production systems that contributed significant dietary inputs were present in the Ñanchoc region by 8000
14
C yr B.P. Starch grain studies of dental remains document plants and edible parts of them not normally preserved in archaeological records and can assume primary roles as direct indicators of ancient human diets and agriculture.
AGO1-miR173 complex initiates phased siRNA formation in plants
Authors: Montgomery Taiowa A. , Yoo Seong Jeon , Fahlgren Noah , Gilbert Sunny D. , Howell Miya D. , Sullivan Christopher M. , Alexander Amanda , Nguyen Goretti , Allen Edwards , Ahn Ji Hoon , Carrington James C.
Published: December 2008

MicroRNA (miRNA)-guided cleavage initiates entry of primary transcripts into the transacting siRNA (tasiRNA) biogenesis pathway involving RNA-DEPENDENT RNA POLYMERASE6, DICER-LIKE4, and SUPPRESSOR OF GENE SILENCING3.
Arabidopsis thaliana TAS1
and
TAS2
families yield tasiRNA that form through miR173-guided initiation–cleavage of primary transcripts and target several transcripts encoding pentatricopeptide repeat proteins and proteins of unknown function. Here, the
TAS1c
locus was modified to produce synthetic (syn) tasiRNA to target an endogenous transcript encoding PHYTOENE DESATURASE and used to analyze the role of miR173 in routing of transcripts through the tasiRNA pathway. miR173 was unique from other miRNAs in its ability to initiate
TAS1c
-based syn-tasiRNA formation. A single miR173 target site was sufficient to route non-
TAS
transcripts into the pathway to yield phased siRNA. We also show that miR173 functions in association with ARGONAUTE 1 (AGO1) during
TAS1
and
TAS2
tasiRNA formation, and we provide data indicating that the miR173–AGO1 complex possesses unique functionality that many other miRNA–AGO1 complexes lack.
Paradoxical effects of increased expression of PGC-1α on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism
Authors: Choi Cheol Soo , Befroy Douglas E. , Codella Roberto , Kim Sheene , Reznick Richard M. , Hwang Yu-Jin , Liu Zhen-Xiang , Lee Hui-Young , Distefano Alberto , Samuel Varman T. , Zhang Dongyan , Cline Gary W. , Handschin Christoph , Lin Jiandie , Petersen Kitt F. , Spiegelman Bruce M. , Shulman Gerald I.
Published: December 2008

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α has been shown to play critical roles in regulating mitochondria biogenesis, respiration, and muscle oxidative phenotype. Furthermore, reductions in the expression of PGC-1α in muscle have been implicated in the pathogenesis of type 2 diabetes. To determine the effect of increased muscle-specific PGC-1α expression on muscle mitochondrial function and glucose and lipid metabolism in vivo, we examined body composition, energy balance, and liver and muscle insulin sensitivity by hyperinsulinemic-euglycemic clamp studies and muscle energetics by using
31
P magnetic resonance spectroscopy in transgenic mice. Increased expression of PGC-1α in muscle resulted in a 2.4-fold increase in mitochondrial density, which was associated with an ≈60% increase in the unidirectional rate of ATP synthesis. Surprisingly, there was no effect of increased muscle PGC-1α expression on whole-body energy expenditure, and PGC-1α transgenic mice were more prone to fat-induced insulin resistance because of decreased insulin-stimulated muscle glucose uptake. The reduced insulin-stimulated muscle glucose uptake could most likely be attributed to a relative increase in fatty acid delivery/triglyceride reesterfication, as reflected by increased expression of CD36, acyl-CoA:diacylglycerol acyltransferase1, and mitochondrial acyl-CoA:glycerol-
sn
-3-phosphate acyltransferase, that may have exceeded mitochondrial fatty acid oxidation, resulting in increased intracellular lipid accumulation and an increase in the membrane to cytosol diacylglycerol content. This, in turn, caused activation of PKCθ, decreased insulin signaling at the level of insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, and skeletal muscle insulin resistance.
Genetic architecture of complex traits: Large phenotypic effects and pervasive epistasis
Authors: Shao Haifeng , Burrage Lindsay C. , Sinasac David S. , Hill Annie E. , Ernest Sheila R. , O'Brien William , Courtland Hayden-William , Jepsen Karl J. , Kirby Andrew , Kulbokas E. J. , Daly Mark J. , Broman Karl W. , Lander Eric S. , Nadeau Joseph H.
Published: December 2008

The genetic architecture of complex traits underlying physiology and disease in most organisms remains elusive. We still know little about the number of genes that underlie these traits, the magnitude of their effects, or the extent to which they interact. Chromosome substitution strains (CSSs) enable statistically powerful studies based on testing engineered inbred strains that have single, unique, and nonoverlapping genetic differences, thereby providing measures of phenotypic effects that are attributable to individual chromosomes. Here, we report a study of phenotypic effects and gene interactions for 90 blood, bone, and metabolic traits in a mouse CSS panel and 54 traits in a rat CSS panel. Two key observations emerge about the genetic architecture of these traits. First, the traits tend to be highly polygenic: across the genome, many individual chromosome substitutions each had significant phenotypic effects and, within each of the chromosomes studied, multiple distinct loci were found. Second, strong epistasis was found among the individual chromosomes. Specifically, individual chromosome substitutions often conferred surprisingly large effects (often a substantial fraction of the entire phenotypic difference between the parental strains), with the result that the sum of these individual effects often dramatically exceeded the difference between the parental strains. We suggest that strong, pervasive epistasis may reflect the presence of several phenotypically-buffered physiological states. These results have implications for identification of complex trait genes, developmental and physiological studies of phenotypic variation, and opportunities to engineer phenotypic outcomes in complex biological systems.
Hardware Accelerated Segmentation of Complex Volumetric Filament Networks
Authors: Mayerich David , Keyser John
Published: December 2008

We present a framework for segmenting and storing filament networks from scalar volume data. Filament networks are encountered more and more commonly in biomedical imaging due to advances in high-throughput microscopy. These data sets are characterized by a complex volumetric network of thin filaments embedded in a scalar volume field. High-throughput microscopy volumes are also difficult to manage since they can require several terabytes of storage, even though the total volume of the embedded structure is much smaller. Filaments in microscopy data sets are difficult to segment because their diameter is often near the sampling resolution of the microscope, yet these networks can span large regions of the data set. We describe a novel method to trace filaments through scalar volume data sets that is robust to both noisy and undersampled data. We use graphics hardware to accelerate the tracing algorithm, making it more useful for large data sets. After the initial network is traced, we use an efficient encoding scheme to store volumetric data pertaining to the network.
The Promotion of Children's and Adolescents’ Social Participation in Italy and Scotland
Authors: Rossi Elisa , Baraldi Claudio
Published: December 2008

This article presents the theoretical framework, methodology and the main results of a comparative research on the promotion of children's social participation in Italy and Scotland, which was based on politicians’, managers’ and practitioners’ representations. Promotion of participation here is considered a form of social intervention in which adults construct and treat children as citizens entitled to be involved in decision‐making processes, due to their competence in self‐expression and making choices. The study revealed a coexistence of different images of childhood and social intervention, as well as some interesting differences and similarities between the two socio‐cultural contexts.
The Value of Play: Constructions of Play in Government Policy in England*
Authors: Powell Sacha
Published: December 2008

This article reports one aspect of the findings from an assessment of the impact of national policies on children’s opportunities for play in England, which was commissioned and funded by the Children’s Play Council, London. Systematic analysis of policy documents and interviews with participants from local authorities and the voluntary sector revealed that the (Labour) Government does not promote a consistent conceptualisation of play in England. While some policy documents emphasise play’s instrumental value and potential contributions to the priorities of government departments, others refer to its intrinsic value. In both cases, however, such constructions of play form a discourse that controls where and how children may play. This inconsistency has led to gaps in the mechanisms for delivery of extensive, sustainable and equitable play opportunities across the country.
Predictors of serious complications due to Clostridium difficile infection
Authors: GUJJA D. , FRIEDENBERG F. K.
Published: December 2008

Background  Identifying individuals with severe Clostridium difficile infection (CDI) at risk for major complications has become an important objective. Presence of clinical variables that predict complications from CDI would have the potential to strongly influence management.

Aim  To determine which clinical variables predict complications from CDI.

Methods  Cross‐sectional study of all individuals admitted to Temple University Hospital between 12/1/03 and 7/1/08 with the primary discharge diagnosis of CDI were eligible. Only patients experiencing their first episode of CDI were included. Abstracted data included demographic, physiological, laboratory, radiological, endoscopic, pharmacy and outcome data. Response was categorized as none, partial or complete. Complications attributed to CDI were defined as colon resection or death.

Results  Overall 32 of 200 patients (16%) experienced a complication due to CDI including death (n = 20) and colectomy (n = 12). White blood cell count above 30,000 cells/mm3 (OR = 4.06; 95% CI, 1.28–12.87) and a rise in the creatinine to over 50% above baseline (OR = 7.13; 95% CI, 3.05–16.68) predicted a complication. AROC for percent rise in serum creatinine was 0.73 (95% CI: 0.64–0.85) and 0.62 (95% CI: 0.58–0.80) for white blood cell count.

Conclusions  Severe white blood cell count elevation and a rise in the creatinine to over 50% above baseline are important independent predictors of serious adverse events due to CDI. These patients likely would benefit from more intensive care and early surgical consultation.
Manufacturing of human placenta‐derived mesenchymal stem cells for clinical trials
Authors: Brooke Gary , Rossetti Tony , Pelekanos Rebecca , Ilic Nina , Murray Patricia , Hancock Sonia , Antonenas Vicki , Huang Gillian , Gottlieb David , Bradstock Ken , Atkinson Kerry
Published: December 2008

Mesenchymal stem cells (MSC) are being used increasingly in clinical trials for a range of regenerative and inflammatory diseases. Bone marrow is the traditional source but is relatively inaccessible in large volume. MSC have now been derived from tissues other than bone marrow including placenta and adipose tissue. We have used placenta obtained after delivery as a source of MSC and have been unable to detect any marked differences from marrow‐derived MSC in terms of cell surface phenotype, chemokine receptor display, mesodermal differentiation capacity or immunosuppressive ability. This report described our manufacturing process for isolating and expanding placenta‐derived human MSC and their safe infusion into the first patient in a clinical trial program of human placenta‐derived MSC.
T regulatory cells distinguish two types of primary hypophysitis
Authors: Mirocha S , Elagin R B , Salamat S , Jaume J C
Published: December 2008

Numerous cases of primary hypophysitis have been described over the past 25 years with, however, little insight into the cause(s) of this disease. In order to guide treatment, a better understanding of the pathogenesis is needed. We studied the pathogenesis of primary hypophysitis by analysing systematically the immune response at the pituitary tissue level of consecutive cases of ‘lymphocytic’ hypophysitis who underwent pituitary biopsy. In order to investigate further the pathogenesis of their diseases we characterized two cases at clinical, cellular and molecular levels. We show here, for the first time, that lymphocytic hypophysitis probably encompasses at least two separate entities. One entity, in agreement with the classical description of lymphocytic hypophysitis, demonstrates an autoimmune process with T helper 17 cell dominance and lack of T regulatory cells. The other entity represents a process in which T regulatory cells seem to control the immune response, which may not be self- but foreign-targeted. Our data suggest that it may be necessary to biopsy suspected primary hypophysitis and to analyse pituitary tissue with immune markers to guide treatment. Based on our results, hypophysitis driven by an immune homeostatic process should not be treated with immunosuppression, while autoimmune-defined hypophysitis may benefit from it. We show here for the first time two different pathogenic processes classified under one disease type and how to distinguish them. Because of our findings, changes in current diagnostic and therapeutic approaches may need to be considered.
A critical appraisal of erectile function in animal models of diabetes mellitus
Authors: Gur Serap , Kadowitz Philip J. , Hellstrom Wayne J. G.
Published: December 2008

The study of erectile function in diabetic animal models has revealed physiological alterations in neural, vascular, hormonal and endothelial function. The aims of this review are to further elucidate pathophysiological changes induced by diabetes mellitus and to introduce new concepts in the study of erectile dysfunction (ED) in animal models. The recognized pathophysiological mechanisms causing diabetic ED include oxidative stress and hormonal imbalance. The evolving treatments for ED include advanced glycosylated endproduct (AGE) inhibitors, phosphodiesterase type 5 inhibitors, protein kinase C (PKC) inhibitors, hormone replacement, and gene transfer techniques. Our current understanding of how these multiple pathophysiological mechanisms contribute to ED is discussed. In this review, diabetic animal model studies have documented that oxidative stress is a pre‐eminent pathophysiological mechanism and several anti‐oxidants, such as α‐lipoic acid, vitamin E, sodium selenate, melatonin, and ascorbic acid, reverse both neurogenic and endothelial dysfunction in diabetic models. Further, the peroxynitrite decomposition catalyst – FeTMPyP, PKCβ selective inhibitor – LY333531, IkappaB kinase 2 inhibitor – AS602868, AGE inhibitors – aminoguanidine and ALT‐711 show promise by exploring different cellular mechanisms in treating diabetic problems. A number of vectors have been used to insert genes to increase the expression of nitric oxide synthase, superoxide dismutase, maxi‐K channel (hSlo), neurotrophin‐3, and vasoactive intestinal polypeptide for the treatment of erectile function. Further investigation of the hormonal treatment of diabetes associated with hypogonadism may improve sildenafil responsiveness in diabetic patients. We are optimistic that novel prevention and treatment strategies for diabetic ED are on the horizon.
Retracted: Effects of exposure to a mobile phone on testicular function and structure in adult rabbit
Authors: Salama Nader , Kishimoto Tomoteru , Kanayama Hiro‐omi
Published: December 2008

The accumulating effects of exposure to electromagnetic radiation emitted by a conventional mobile phone (standby position) on the testicular function and structure are not yet fully investigated. To study these effects longitudinally, a total of 24 adult male rabbits were randomly and equally divided into three groups. Rabbits in the first (phone) group were exposed, in specially designed cages, to radio frequency emitted from the mobile phone (800 MHz) in a standby position opposite to that of testes for 8 h daily for 12 weeks. The second group consisted of the stress controls which were kept in the same kind of cages to appreciate any cage‐induced anxiety. The third group included the ordinary controls which were kept in the conventional roomy cages. Semen analysis and sperm function tests (viability, hypo‐osmotic swelling and acridine orange) were conducted weekly. Histological testicular sections and serum total testosterone were also evaluated. A drop in the sperm concentration appeared in the phone group at week 6. This became statistically significant at week 8, compared with the two control (stress and ordinary) groups (133, 339 and 356 × 106/mL, respectively) and to the initial sperm count (341 × 106/mL) of this group. Motile sperm population showed similarity amongst the three study groups until week 10 when it declined significantly, and thereafter in the phone and stress control groups, with more significant decline in the phone animals (50, 61 and 72.4%, respectively). Histological examination showed also a significant decrease in the diameter of seminiferous tubules in the phone group vs. the stress and ordinary controls (191 μm vs. 206 and 226 μm, respectively). The other study points did not show any difference. In conclusion, low intensity pulsed radio frequency emitted by a conventional mobile phone kept in the standby position could affect the testicular function and structure in the adult rabbit.
Biological and clinical significance of DNA damage in the male germ line
Authors: Aitken R. John , De Iuliis Geoffry N. , McLachlan Robert I.
Published: December 2008

DNA damage is a common feature of human spermatozoa with purported links to poor rates of conception, impaired embryonic development, an increased incidence of miscarriage and the appearance of various kinds of morbidity in the offspring including childhood cancer. However, difficulties in interpretation arise, because these associations are not consistently observed across all data sets. Such inconsistency reflects the inherent complexity of the reproductive process, large variations in sample size, differences in patient selection, inadequate study design as well as inter‐individual differences in the type of DNA damage being detected and the effectiveness of repair mechanisms in the oocyte. This review considers the type, source and measurement of DNA damage in human spermatozoa. It also addresses the clinical utility of the information generated in such studies, and highlights areas where further research is needed to bridge the gap between an intriguing biological phenomenon and the evidence‐based clinical management of male patients characterized by high levels of DNA damage in their spermatozoa.
Rectal hyposensitivity: pathophysiological mechanisms
Authors: Gladman M. A. , Aziz Q. , Scott S. M. , Williams N. S. , Lunniss P. J.
Published: December 2008

Abstract  Rectal hyposensitivity (RH) relates to a diminished perception of rectal distension. It may occur due to afferent nerve dysfunction and/or secondary to abnormal structural or biomechanical properties of the rectum. The aim of this study was to determine the contribution of these underlying pathophysiological mechanisms by systematically evaluating rectal diameter, compliance and afferent nerve sensitivity in patients with RH, using methodology employed in clinical practice. The study population comprised 45 (33 women; median age 48, range 25–72 years) constipated patients (Rome II criteria) with RH and 20 with normal rectal sensitivity on balloon distension and 20 healthy volunteers. Rectal diameter was measured at minimum distending pressure during isobaric distension under fluoroscopic screening. Rectal compliance was assessed during phasic isobaric distension by measuring the slope of the pressure–volume curve. Electrical stimulation of the rectal mucosa was employed to determine afferent nerve function. Values were compared to normal ranges established in healthy volunteers. The upper limits of normal for rectal diameter, compliance and electrosensitivity were 6.3 cm, 17.9 mL mmHg−1 and 21.3 mA respectively. Among patients with RH, rectal diameter, but not compliance, was increased above the normal range (megarectum) in seven patients (16%), two of whom had elevated electrosensitivity thresholds. Rectal diameter and compliance were elevated in 23 patients (51%), nine of whom had elevated electrosensitivity thresholds. The remaining 15 patients (33%) with RH had normal rectal compliance and diameter, all of whom had elevated electrosensitivity thresholds. Two‐third of the patients with RH on simple balloon distension have elevated rectal compliance and/or diameter, suggesting that impaired perception of rectal distension is due to inadequate stimulation of the rectal afferent pathway. However, a proportion of such patients also appear to have impaired nerve function. In the remaining one‐third of the patients, rectal diameter and compliance are normal, while electrosensitivity thresholds are elevated, suggestive of true impaired afferent nerve function. Identification of these subgroups of patients with RH may have implications regarding their management.
The role of light in soybean seed filling metabolism
Authors: Allen Doug K. , Ohlrogge John B. , Shachar‐Hill Yair
Published: December 2008

Soybean (Glycine max) yields high levels of both protein and oil, making it one of the most versatile and important crops in the world. Light has been implicated in the physiology of developing green seeds including soybeans but its roles are not quantitatively understood. We have determined the light levels reaching growing soybean embryos under field conditions and report detailed redox and energy balance analyses for them. Direct flux measurements and labeling patterns for multiple labeling experiments including [U‐13C6]‐glucose, [U‐13C5]‐glutamine, the combination of [U‐14C12]‐sucrose + [U‐14C6]‐glucose + [U‐14C5]‐glutamine + [U‐14C4]‐asparagine, or 14CO2 labeling were performed at different light levels to give further insight into green embryo metabolism during seed filling and to develop and validate a flux map. Labeling patterns (protein amino acids, triacylglycerol fatty acids, starch, cell wall, protein glycan monomers, organic acids), uptake fluxes (glutamine, asparagine, sucrose, glucose), fluxes to biomass (protein amino acids, oil), and respiratory fluxes (CO2, O2) were established by a combination of gas chromatography‐mass spectrometry, 13C‐ and 1H‐NMR, scintillation counting, HPLC, gas chromatography‐flame ionization detection, C:N and amino acid analyses, and infrared gas analysis, yielding over 750 measurements of metabolism. Our results show: (i) that developing soybeans receive low but significant light levels that influence growth and metabolism; (ii) a role for light in generating ATP but not net reductant during seed filling; (iii) that flux through Rubisco contributes to carbon conversion efficiency through generation of 3‐phosphoglycerate; and (iv) a larger contribution of amino acid carbon to fatty acid synthesis than in other oilseeds analyzed to date.
A BAHD acyltransferase is expressed in the tapetum of Arabidopsis anthers and is involved in the synthesis of hydroxycinnamoyl spermidines
Authors: Grienenberger Etienne , Besseau Sébastien , Geoffroy Pierrette , Debayle Delphine , Heintz Dimitri , Lapierre Catherine , Pollet Brigitte , Heitz Thierry , Legrand Michel
Published: December 2008

BAHD acyltransferases catalyze the acylation of many plant secondary metabolites. We characterized the function of At2g19070, a member of the BAHD gene family of Arabidopsis thaliana. The acyltransferase gene was shown to be specifically expressed in anther tapetum cells in the early stages of flower development. The impact of gene repression was studied in RNAi plants and in a knockout (KO) mutant line. Immunoblotting with a specific antiserum raised against the recombinant protein was used to evaluate the accumulation of At2g19070 gene product in flowers of various Arabidopsis genotypes including the KO and RNAi lines, the male sterile mutant ms1 and transformants overexpressing the acyltransferase gene. Metabolic profiling of flower bud tissues from these genetic backgrounds demonstrated a positive correlation between the accumulation of acyltransferase protein and the quantities of metabolites that were putatively identified by tandem mass spectrometry as N1,N5,N10‐trihydroxyferuloyl spermidine and N1,N5‐dihydroxyferuloyl‐N10‐sinapoyl spermidine. These products, deposited in pollen coat, can be readily extracted by pollen wash and were shown to be responsible for pollen autofluorescence. The activity of the recombinant enzyme produced in bacteria was assayed with various hydroxycinnamoyl‐CoA esters and polyamines as donor and acceptor substrates, respectively. Feruloyl‐CoA and spermidine proved the best substrates, and the enzyme has therefore been named spermidine hydroxycinnamoyl transferase (SHT). A methyltransferase gene (At1g67990) which co‐regulated with SHT during flower development, was shown to be involved in the O‐methylation of spermidine conjugates by analyzing the consequences of its repression in RNAi plants and by characterizing the methylation activity of the recombinant enzyme.
The Search for a Human Equivalent of the Mouse T‐Locus ‐ Negative Results from a Study of HL—A Types in Spina Bifida
Authors: BOBROW MARTIN , BODMER JULIA G. , BODMER W. F. , MCDEVITT H. O. , LORBER J. , SwiFT P.
Published: December 2008

The spina bifida/anencephaly complex in man in some ways resembles the effects of T‐locus mutants in the mouse. To test the hypothesis that these entities are genetically related, HL‐A typing was performed in families with multiple cases of central nervous system abnormality. No evidence of linkage was found between HL‐A type and the congenital malformation.
The Assessment of Histocompatibility by Mixed Lymphocyte Reaction as Measured by the Macrophage Electrophoretic Mobility (MEM) Test
Authors: SHENTON B. K. , ULDALL P. R. , SWINNEY J. , FIELD E. J.
Published: December 2008

The mixed lymphocyte reaction (MLR) between donor and recipienTlymphocytes has been measured by the macrophage electrophoretic mobility (MEM) test and the modified (MOD‐MEM) test. Its value as a measure of compatibility has been assessed by comparison with conventional HL‐A serotyping and with the outcome of renal transplantation.

Thirty‐six living donor/recipient pairs and 59 cadaver donor/recipient pairs for transplantation have been studied. Whilst uniovular twins gave lymphocyte interactions, measured as macrophage slowings of about 1 %, the slowing produced by paired allogeneic lymphocytes ranged from 2 % to 26 % depending on the number of HL—A matches.

The test measurement of lymphocytic interaction was significantly correlated with histocompatibility measured by HL—A serotyping, in both living and cadaver donors. One way MEM‐MLR showed the dominant role of the second HL—A sublocus in mixed lymphocyte reactivity. The long term success of the renal graft correlated with the pre‐transplant initial reaction between donor and recipienTlymphocytes.

The test has advantages in the field of human histocompatibility assessment since no particular reference to individual antigens is made and it may be performed in a matter of hours.
On the Localization of the Gb Locus within the MHS Region of Chromosome No. 6
Authors: TEISBERG P. , OLAISEN B. , GEDDE‐DAHL T. , THORSBY E.
Published: December 2008

Further data on the Gb ‐ HL‐A linkage relationship are presented. All three GBG informative recombinants investigated are Gb ‐ first HL—A recombinants; therefore Gb must be situated on the second HL‐A side of the first HL—A locus. Ninety additional apparently Gb ‐ HL‐A non‐recombinant offspring from 23 matings indicate that the Gb locus is situated in close proximity to the second HL‐A locus.
MLG Results among Unrelated can be Predicted
Authors: JøRGENSEN F. , LAMM L. U. , KTSSMEYER‐NIELSEN F.
Published: December 2008

Typing for LD determinants which has been practicable for some time is shown to be very predictive for the MLC response between unrelated, since LD identical individuals ‐ selected and paired solely on the basis of LD typing ‐ mutually show very low or no MLG reaction.
Definition of 17 Rhesus Monkey Histocompatibility Antigens, Including One New Antigen*
Authors: Maurer Bruce A. , Jones Judy A. , Neefe John R.
Published: December 2008

The lymphocytotoxic activity of 144 rhesus alloantisera was evaluated in 112 unrelated rhesus monkeys and 33 pedigreed rhesus families. This study was conducted using a standard complement‐dependent microcytotoxicity assay. A computer‐assisted X2 analysis of the reactivity of these sera in the unrelated monkeys generated 23 groups of highly correlated antisera. The two‐locus model of the mammalian major histocompatibility complex was assumed for the monkey, and genetic criteria for RhLA antigens were determined prior to study. Seventeen groups of antisera met these predetermined criteria. Six were products of the B locus and 11 were products of the A locus. Sixteen were similar or identical to antigens previously described by us or by Balner and coworkers in The Netherlands. One has not been previously described. A frequency analysis indicated that these 17 antigens represented approximately 74% of the total expression of these two loci.
Daily Monitoring of the Immune Response to Various Allografts in Rats
Authors: Smart I. J. , Boyle W. , Morris P. J.
Published: December 2008

The appearance of activated lymphocytes and antibodies in the circulation of rats was monitored following allogeneic kidney, skin, or combined skin‐spleen transplants. Lymphocyte activation was measured by 3H‐thymidine incorporation, and antibody by a hemolytic assay. These assays have been developed so that small samples of blood could be used, thus maintaining recipient survival and allowing for daily correlation between the response observed and the fate of the graft. These responses were detected after allogeneic transplantation in two recipient strains, but not following isogeneic renal or skin transplantation in either strain. The relative levels, time of onset and persistence of lymphocyte proliferation and of hemolytic antibody were found to differ substantially for the three different kinds of allografts. In general, these studies have demonstrated the validity of using the lymphocyte proliferative and humoral responses together as indicators of a current immune response against allogeneic renal transplants.
Localization of Genetic Control in Mice over Response to Liver‐Specific F Antigen
Authors: Long G. W. , Bernard C. C. A. , Mackay I. R. , Whittingham Senga , Bhathal P. S.
Published: December 2008

Antibody production to the liver‐specific F antigen was tested in recombinant strains of mice of different H‐2 types to determine whether a histocompatibility‐linked immune response (Ir) gene controlled responsiveness to this antigen. Responsiveness was found to be controlled by an Ir gene located in the K end (K and/or I‐A subregions) of the H‐2 complex.
HLA System and Balkan Endemic Nephropathy: (A collective study with the collaboration of all participants in the HLA Workshop‐Sofia 1976)
Authors: Minev M. , Mikhaylov T. , Katelan A. , Nyulassy S. , Menzel G.
Published: December 2008

Balkan endemic nephropathy, a fatal family disease with unknown aetiology and pathogenesis is typical for three neighbouring regions in Bulgaria, Yugoslavia and Rumania. HLA typing of 180 patients from the endemic area in Bulgaria was done and the antigen frequencies were compared with 1264 healthy controls. An increased frequency (P < 0.001) of the antigen HLA‐B18 in the patients was demonstrated.
Type IIa Hyperlipoproteinemia and the HLA System
Authors: Raffoux C. , Pointel J. P. , Drouin P. , Streiff F. , Debry G. , Sauvanet J. P.
Published: December 2008

The comparative study of a control group made up of 340 healthy subjects, a group of 100 unrelated patients, all showing signs of type II hyperlipoproteinemia and a family of 15 members covering three successive generations, brings to light the highly significant increase of the recurrence of HLA Bw17 antigen and the increase in frequency of HLA Bw35 antigen.
HLA and Mycobacterial Infection: Increased Frequency of B8 in Japanese Leprosy*
Authors: Takata Hajime , Sada Masaharu , Ozawa Shinji , Sekiguchi Susumu
Published: December 2008

A total of 60 leprosy patients, 28 of lepromatous and 32 of tuberculoid form, and 70 active tuberculosis patients was compared with a control of 184 for 34 HLA specificities. The most interesting finding was an increased frequency (10.0%) for HLA‐B8 (corrected P= 0.062, relative risk = 20.3) in the leprosy patients as compared with the control group, despite the fact that the frequency of HLA‐B8 was extremely low in Japanese. Furthermore, all leprosy patients with B8 had leprous member(s) in their family.
A Genetic Study of Behqet Disease in Israel
Authors: Brautbar Chaim , Chajek Tova , Ben‐Tuvia Sheila , Lamm Lars , Cohen Tirza
Published: December 2008

The frequency of HLA‐B5 in 24 Israeli Behçet disease (BD) patients from various subpopulations was significantly greater than in 615 control individuals (P < 0.003). The relative risk for a B5 carrier to develop BD was calculated to be 5.0. Six patients were offspring of consanguineous marriages, which is not unexpected in the populations studied. Five of the patients had only one HLA‐B antigen, which in four cases was B5. Two of the latter were B5 homozygotes, indicating a possible greater susceptibility. This study confirms the reported association between BD and HLA‐B5 in a population not previously investigated. Furthermore, these data support the suggestion that B5 is associated with BD in populations deriving from the Mediterranean Basin, the Middle East and Far East.
Appearance and Evolution of Anti‐Da (B Cell‐Specific) Antibodies after Planned Immunizations
Authors: Belvedere Mariaclara , Richiardi Patricia , Savi Mario , Curtoni Emilio S. , Carbonara Angelo O. , Ceppellini Ruggero
Published: December 2008

Appearance and evolution of anti‐Da antibodies has been followed in eight volunteers immunized by whole blood transfusions or leukocyte intradermal injections from a single donor incompatible for HLA—A,—B,—C and—D specificities. Several unabsorbed bleedings from each recipient were studied against the specific immunizer with three different complement‐dependent lymphocytotoxicity (CdL) techniques: (1) standard NIH CdL on total peripheral blood lymphocytes (PBL); (2) VII Workshop standard CdL technique on B cell‐enriched suspensions; (3) β2 microglobulin blanketing test (“bb” test) on B cells.

Results obtained with the “bb” test were confirmed with platelet‐absorbed sera. The “bb” and the absorbed sera allow discrimination between anti‐Da and anti‐HLA—A,—B,—C antibodies.

Stage of appearance and evolution are rather similar for an anti‐HLA—A,—B,—C and anti‐Da. An early appearance of antibodies positive only against B cells is due to weak anti‐HLA—A,—B antibodies which react better with B cells than with total PBL. Immunogenicity of Da antigens seems to be of the same order as HLA—A, and—B. In fact, Da reactivity was present in all eight recipients studied. These reactivities always segregated in families with these HLA haplotypes. On a small panel of unrelated D‐typed donors, three sera showed a significant positive association with D alleles.
The Major Histocompatibility Complex of Rhesus Monkeys IX. Current Concepts of Serology and Genetics of Ia Antigensa
Authors: Roger J. H. , van Vreeswijk W. , D'Amaro J. , Balner H.
Published: December 2008

Eleven Ia or B‐cell specificities of rhesus monkeys have been serologically identified. They are probably all controlled by the RhLA complex, but, according to results of a large population and family study, only five or six can be placed in a segregant series, designated as Ia1. Data from recombinant offspring in two rhesus families place the Ia1 locus in the close vicinity of the D or major MLC locus within RhLA. The genetic control of the Ia antigens not defined by the Ia1 locus has not yet been clarified.
Modification of HLA Antigens in Patients with Malignancies Following Hormone Therapy
Authors: Májský A. , Abrahámová J.
Published: December 2008

In 23 out of 39 patients with various malignancies, treated with hormones (Prednison, Agostilben, Agovirin, separately, or combined; Prednison plus another hormone) modification of HLA antigens was established. Out of 51 patients with hitherto untreated malignancies HLA modification was demonstrated in 12 cases. This variation is statistically significant (P= 0.0006), and suggests hormonal therapy to be one of the causes of HLA modification in malignant tumors. The serological pattern of HLA modification varied: in five patients lymphocyte poiyreactdvity; in 10, loss of HLA antigens; in six, weakening of HLA antigens and in two, transformation of HLA—A2 in HLA—A28. The modification was transient in character. It occurred most frequently following administration of Prednison, or Prednison combined with some other hormone, and was unrelated to drug dosage.
Primary Affective Disorders and HLA Antigens
Authors: Májský A. , Zvolský P. , Dvořáková M.
Published: December 2008

In 125 patients with various types of primary affective disorders, 27 HLA antigens of the A, B and C loci were examined. Bw40 occurred more frequently in the primary form (20.83% against 7.64% in controls) and Cw4 in the unipolar form (25%) and, in disease in general, 16%, against 9.58% in controls. Following correction, however, these differences are statistically insignificant.
HLA Polymorphism in Israel: 2. Israeli Jews originating from Russia
Authors: Brautbar C. , Zamir R. , Efter T. , Gazit E.
Published: December 2008

HLA typing of 123 Israeli Jews of Russian origin showed a high frequency for HLA—A1, A2, Aw19 and B14, Bw16 and Bw35 of the A and B loci, respectively. The most frequently occuring haplotypes were (A1, B17), (Aw25, B18), (Aw26, Bw16), (Aw19, B13), (Aw23, B5) and (Aw25, Bw35). This study reveals a striking resemblance in the distribution of frequencies of HLA alleles and haplotypes between Russian Jews and two other East European Jewish communities (presented in this issue) of Polish and Rumanian origin.
HLA Polymorphism in Israel: 4. Israeli Jews originating from Rumania
Authors: Zamir R. , Brautbar C. , Mizrachi Y. , Yehoshua H. , Gazit E.
Published: December 2008

The frequencies of 29 HLA antigens of the A and B loci were studied in 130 Israeli Jews originating from Rumania. The antigens A1, A2, Aw19 and B14, Bw16 and Bw35 occurred with the highest frequencies. The most common haplotypes were (A1, B17), (Aw26, Bw16) and (A28. Bw22), These results are similar to those observed in Polish and Russian Jews.
Can Anti HLA‐A and ‐B Antibodies Inhibit the MLC Test?
Authors: Jonker Margreet , J. J. van Rood
Published: December 2008

Eleven lymphocytotoxic pregnancy sera were tested for inhibition in the MLC test. Responder inhibition and stimulator inhibition were analyzed separately by using cells from the serum producer as stimulator and responder respectively. Only three sera showed inhibition of responder function, whereas all sera showed inhibition of stimulator function. The specificity of the latter inhibition was at least in part attributable to antibodies directed to specificities other than B‐cell specificities (presumed to be coded for in the HLA—D region). This was deduced from the fact that platelet eluates devoid of anti B‐cell antibodies effectively inhibited in MLC.
Tissue Typing of Cells in Culture. II. Histocompatibility Typing of Diploid Fibroblastic Cultures by the Mixed Hemadsorption (MH) Test
Authors: Espmark Åke , Möller Erna
Published: December 2008

Skin fibroblasts derived from persons who had been HLA—typed by conventional lymphocyto‐toxocity tests were subjected to HLA—typing by the mixed hemadsorption (MH) test. The agreement between the two methods was good, provided sera for the MH test were carefully selected. Minor discrepancies found in this study can probably be corrected by further serum selection.

There was no difficulty in typing late passages of cultured diploid cells (22 doublings) and in fact it was easier to type a culture at the 33rd doubling than at the 11th. Thus no signs of disappearance of HLA—antigens were seen in these tests.
Tissue Typing of Cells in Culture. III. HLA Antigens of Established Human Cell Lines. Attempts at Typing by the Mixed Hemadsorption Technique
Authors: Espmark J. Åke , Ahlqvist‐Roth Lena , Säme Lena , Persson Anita
Published: December 2008

Thirty established cell lines from solid human tumors were typed by the mixed hemadsorption technique with respect to the HLA—A and HLA—B and partly also the HLA—C series. All cultures exhibited unique antigenic patterns. The discriminatory potential was further increased very much taking into consideration one as yet undefined antigen series tentatively named Ek‐1 to Ek‐11. Sixteen cell lines not designated as HeLa cells but on various non‐immunological indications suspected to be HeLa cell contaminants, all gave, with our present test, the same antigenic composition as HeLa cells or clones thereof. The mixed hemadsorption reaction is a highly sensitive and convenient method for immunological typing of cells in monolayer cultures. Some important implications of this are discussed.
Tissue Typing of Cells in Culture. IV. Cell Surface Antigens of Tumor Cell Lines, not Obviously Belonging to the HLA‐System
Authors: Espmark Åke
Published: December 2008

Studies on the HLA pattern of several human tumor cell lines by the mixed hemadsorption test and also studies on the discriminative patterns formed by a collection of sera on a number of cell lines and diploid cells have been reported elsewhere. It was noted during these studies that some sera reacted in a fashion indicating that they did not represent any of the HLA‐A or ‐B series and probably not the HLA—C series either. The corresponding antigenic determinants were tentatively designated Ek‐1 to Ek‐11. The pattern of these antigens among the cell lines is given in a table and it seems apparent that the Ek‐series considerably increases the cell identification potential of the typing results. So far, five of the sera determining the Ek‐antigens have failed to be blocked by anti‐β‐2‐microglobulin, indicating that the antigens do not belong to the HLA—A, B or C series. Preparatory work for HLA—D typing is under way.
Genetic Control of B‐Cell Alloantigens: Evidence for Gene(s) Linked to the HLA—A Locus
Authors: Abelson Leslie D. , Mann Dean L.
Published: December 2008

Families with known HLA recombinant individuals were typed for B‐lymphocyte alloantigens. The B‐cell alloantigens were found to be inherited with the intact HLA haplotypes. However, the results of the typing of the recombinant individuals indicated that specific antigens are associated with the HLA—A locus and/or with the HLA—B locus. These studies indicate that more than one gene initiates the expression of these antigens and that some of these genes may map between the HLA‐A and HLA‐B loci.
Subdivisions of the HLA—B5 and Bw35 Complex
Authors: Payne R. , Amos B. , Kostyu D. , Engelfriet C. P. , van den Berg‐Loonen P. M. , Curtoni E. S. , Richiardi P.
Published: December 2008

Population studies in 579 individuals, previously phenotyped to be B5 or Bw35, were carried out with 23 HLA antisera defining the B5—Bw35 complex. The inheritance of five subdivisions in this complex, B5.1, B5.2, R5.y, Bw35 and BHR were tested in 23 families. Differing frequencies of these specificities were observed in American Indians, Blacks, Caucasians, Chinese, Filipinos, Japanese and Mexican Americans.
Histocompatibility Antigens in two American Indian Tribes of French Guiana
Authors: Tchen Paul , Bois Etienne , Feingold Nicole , Grenand Franchise , Degos Laurent , Dastot H. , Reboul M.
Published: December 2008

Two South American Indian populations were typed for HLA antigens. In each, the individuals typed were related and their genealogies were known. Determination of their genotypes was done; there seemed to be neither excess nor deficiency in homozygotes. The antigens observed, A2, A9, Aw19.2 (Aw30‐Aw31), A28 for the first locus and B5, Bw15, Bw35, Bw40 for the second locus are in accordance with those previously described for other South American Indians. The two populations belong to the same primary linguistic family Tupi‐Guarani and they live in the same geographic area, but there was no intertribal marriage until recently. Genetic drift can explain the differences observed.
Studies on the Specificity of CML Report from a CML‐Workshop
Authors: Kristensen Tom
Published: December 2008

In a collaboratory study involving eight different laboratories 30 human, mixed lymphocyte culture educated cytotoxic/ymphocytes (CTLs) were identified yielding reproducible cytolysis on allogenic lymphocyte target cells without detectable HLA—A, B (and C) antigenic sharing between stimulator and target cells.

These CTLs were collected in one laboratory (Aarhus) and tested in parallel against a population sample of 100 unrelated, healthy Danes. The testing was only performed once and 11 CTLs did not discriminate in the population, probably due to transportation damage. On the basis of pairwise comparisons between 19 CTLs, three tentative CML‐defined specificities could be recognized. These three groups may have defined monospecific traits of allelic genetic origin as judged by a mutually negative, albeit not significant, correlation and a fit to Hardy‐Weinberg equilibrium.

The concept of determinants other than the serologically defined HLA antigens recognized by some CTLs can thus still be maintained as can the approach to CML typing tested in this workshop.
A Mucoprotein with Colon‐Specific Determinants
Authors: Gold David V. , Miller Frederick
Published: December 2008

The tissue specificity of colonic mucoprotein antigen (CMA) was examined to determine whether the antigen might have a role as a tissue marker. The immunofluorescent technique, using a rabbit anti‐CMA antiserum, was employed to examine a wide range of tissues. Gastrointestinal mucosae as well as non‐gastrointestinal mucin producing tissues were positive; however, non‐gastrointestinal reactivity could be eliminated by the appropriate absorptions. Mucoproteins were purified separately from each gastrointestinal anatomic region and used to absorb the antiserum. This analysis demonstrated the existence of a family of mucoproteins with a common gastrointestinal specific determinant(s). Mucoproteins from neighboring regions, as seen by this antiserum, showed a greater structural similarity than did mucoproteins from distant regions. Absorption of the antiserum with ileal or cecal mucoprotein allowed the detection of a colon specific determinant present on CMA.