bluuebunny/crossref_metadata_2025 huggingface dataset:
A dynamic zone defines interneuron remodeling in the adult neocortex
Authors: Lee Wei-Chung Allen , Chen Jerry L. , Huang Hayden , Leslie Jennifer H. , Amitai Yael , So Peter T. , Nedivi Elly
Published: December 2008

The contribution of structural remodeling to long-term adult brain plasticity is unclear. Here, we investigate features of GABAergic interneuron dendrite dynamics and extract clues regarding its potential role in cortical function and circuit plasticity. We show that remodeling interneurons are contained within a “dynamic zone” corresponding to a superficial strip of layers 2/3, and remodeling dendrites respect the lower border of this zone. Remodeling occurs primarily at the periphery of dendritic fields with addition and retraction of new branch tips. We further show that dendrite remodeling is not intrinsic to a specific interneuron class. These data suggest that interneuron remodeling is not a feature predetermined by genetic lineage, but rather, it is imposed by cortical laminar circuitry. Our findings are consistent with dynamic GABAergic modulation of feedforward and recurrent connections in response to top-down feedback and suggest a structural component to functional plasticity of supragranular neocortical laminae.
The size variance relationship of business firm growth rates
Authors: Riccaboni Massimo , Pammolli Fabio , Buldyrev Sergey V. , Ponta Linda , Stanley H. E.
Published: December 2008

The relationship between the size and the variance of firm growth rates is known to follow an approximate power-law behavior σ(
S
) ≈
S

−β(
S
)

where
S
is the firm size and β(
S
) ≈ 0.2 is an exponent that weakly depends on
S
. Here, we show how a model of proportional growth, which treats firms as classes composed of various numbers of units of variable size, can explain this size-variance dependence. In general, the model predicts that β(
S
) must exhibit a crossover from β(0) = 0 to β(∞) = 1/2. For a realistic set of parameters, β(
S
) is approximately constant and can vary from 0.14 to 0.2 depending on the average number of units in the firm. We test the model with a unique industry-specific database in which firm sales are given in terms of the sum of the sales of all their products. We find that the model is consistent with the empirically observed size-variance relationship.
Phospholipase Cβ3 in mouse and human dorsal root ganglia and spinal cord is a possible target for treatment of neuropathic pain
Authors: Shi Tie-Jun Sten , Liu Su-Xing Leslie , Hammarberg Henrik , Watanabe Masahiko , Xu Zhi-Qing David , Hökfelt Tomas
Published: December 2008

Treatment of neuropathic pain is a major clinical problem. This study shows expression of phospholipase ß3 (PLCß3) in mouse and human DRG neurons, mainly in small ones and mostly with a nonpeptidergic phenotype. After spared nerve injury, the pain threshold was strongly reduced, and systemic treatment of such animals with the unselective PLC inhibitor U73122 caused a rapid and long-lasting (48-h) increase in pain threshold. Thus, inhibition of PLC may provide a way to treat neuropathic pain.
Adenosine in the tuberomammillary nucleus inhibits the histaminergic system via A1receptors and promotes non-rapid eye movement sleep
Authors: Oishi Yo , Huang Zhi-Li , Fredholm Bertil B. , Urade Yoshihiro , Hayaishi Osamu
Published: December 2008

Adenosine has been proposed to promote sleep through A1receptors (A1R's) and/or A2Areceptors in the brain. We previously reported that A2Areceptors mediate the sleep-promoting effect of prostaglandin D2, an endogenous sleep-inducing substance, and that activation of these receptors induces sleep and blockade of them by caffeine results in wakefulness. On the other hand, A1R has been suggested to increase sleep by inhibition of the cholinergic region of the basal forebrain. However, the role and target sites of A1R in sleep–wake regulation remained controversial. In this study, immunohistochemistry revealed that A1R was expressed in histaminergic neurons of the rat tuberomammillary nucleus (TMN).In vivomicrodialysis showed that the histamine release in the frontal cortex was decreased by microinjection into the TMN of N6-cyclopentyladenosine (CPA), an A1R agonist, adenosine or coformycin, an inhibitor of adenosine deaminase, which catabolizes adenosine to inosine. Bilateral injection of CPA into the rat TMN significantly increased the amount and the delta power density of non-rapid eye movement (non-REM; NREM) sleep but did not affect REM sleep. CPA-promoted sleep was observed in WT mice but not in KO mice for A1R or histamine H1receptor, indicating that the NREM sleep promoted by A1R-specific agonist depended on the histaminergic system. Furthermore, the bilateral injection of adenosine or coformycin into the rat TMN increased NREM sleep, which was completely abolished by coadministration of 1,3-dimethyl-8-cyclopenthylxanthine, a selective A1R antagonist. These results indicate that endogenous adenosine in the TMN suppresses the histaminergic system via A1R to promote NREM sleep.
SMRT repression of nuclear receptors controls the adipogenic set point and metabolic homeostasis
Authors: Nofsinger Russell R. , Li Pingping , Hong Suk-Hyun , Jonker Johan W. , Barish Grant D. , Ying Hao , Cheng Sheue-yann , LeBlanc Mathias , Xu Wei , Pei Liming , Kang Yeon-Joo , Nelson Michael , Downes Michael , Yu Ruth T. , Olefsky Jerrold M. , Lee Chih-Hao , Evans Ronald M.
Published: December 2008

The nuclear receptor corepressor, silencing mediator of retinoid and thyroid hormone receptors (SMRT), is recruited by a plethora of transcription factors to mediate lineage and signal-dependent transcriptional repression. We generated a knockin mutation in the receptor interaction domain (RID) of SMRT (SMRT
mRID
) that solely disrupts its interaction with nuclear hormone receptors (NHRs). SMRT
mRID
mice are viable and exhibit no gross developmental abnormalities, demonstrating that the reported lethality of SMRT knockouts is determined by non-NHR transcription factors. However, SMRT
mRID
mice exhibit widespread metabolic defects including reduced respiration, altered insulin sensitivity, and 70% increased adiposity. The latter phenotype is illustrated by the observation that SMRT
mRID
-derived MEFs display a dramatically increased adipogenic capacity and accelerated differentiation rate. Collectively, our results demonstrate that SMRT-RID-dependent repression is a key determinant of the adipogenic set point as well as an integrator of glucose metabolism and whole-body metabolic homeostasis.
MicroRNA regulation of a cancer network: Consequences of the feedback loops involving miR-17-92, E2F, and Myc
Authors: Aguda Baltazar D. , Kim Yangjin , Piper-Hunter Melissa G. , Friedman Avner , Marsh Clay B.
Published: December 2008

The transcription factors E2F and Myc participate in the control of cell proliferation and apoptosis, and can act as oncogenes or tumor suppressors depending on their levels of expression. Positive feedback loops in the regulation of these factors are predicted—and recently shown experimentally—to lead to bistability, which is a phenomenon characterized by the existence of low and high protein levels (“off” and “on” levels, respectively), with sharp transitions between levels being inducible by, for example, changes in growth factor concentrations. E2F and Myc are inhibited at the posttranscriptional step by members of a cluster of microRNAs (miRs) called miR-17-92. In return, E2F and Myc induce the transcription of miR-17-92, thus forming a negative feedback loop in the interaction network. The consequences of the coupling between the E2F/Myc positive feedback loops and the E2F/Myc/miR-17-92 negative feedback loop are analyzed using a mathematical model. The model predicts that miR-17-92 plays a critical role in regulating the position of the off–on switch in E2F/Myc protein levels, and in determining the on levels of these proteins. The model also predicts large-amplitude protein oscillations that coexist with the off steady state levels. Using the concept and model prediction of a “cancer zone,” the oncogenic and tumor suppressor properties of miR-17-92 is demonstrated to parallel the same properties of E2F and Myc.
The powdery mildew fungus Podosphaera fusca (synonym Podosphaera xanthii), a constant threat to cucurbits
Authors: PÉREZ‐GARCÍA ALEJANDRO , ROMERO DIEGO , FERNÁNDEZ‐ORTUÑO DOLORES , LÓPEZ‐RUIZ FRANCISCO , DE VICENTE ANTONIO , TORÉS JUAN A.
Published: December 2008

Numerous vegetable crops are susceptible to powdery mildew, but cucurbits are arguably the group most severely affected. Podosphaera fusca (synonym Podosphaera xanthii) is the main causal agent of cucurbit powdery mildew and one of the most important limiting factors for cucurbit production worldwide. Although great efforts have been invested in disease control, by contrast, many basic aspects of the biology of P. fusca remain unknown.

Taxonomy: Podosphaera fusca (Fr.) Braun & Shishkoff. Kingdom Fungi; Phylum Ascomycota; Subdivision Pezizomycotina; Class Leotiomycetes; Order Erysiphales; Family Erysiphaceae; genus Podosphaera; species fusca.

Identification: Superficial persistent mycelium. Conidia in chains, hyaline, ellipsoid to ovoid or doliform, about 24–40 × 15–22 µm, with cylindrical or cone‐shaped fibrosin bodies, which often germinate from a lateral face and produce a broad, clavate germ tube and cylindrical foot‐cells. Unbranched erect conidiophores. Cleistothecia globose, mostly 70–100 µm in diameter, dark brown/black. One ascus per cleistothecium with eight ascospores.

Host range: Angiosperm species that include several families, such as Asteracea, Cucurbitaceae, Lamiaceae, Scrophulariaceae, Solanaceae and Verbenaceae.

Disease symptoms: White colonies develop on leaf surfaces, petioles and stems. Under favourable environmental conditions, the colonies coalesce and the host tissue becomes chlorotic and usually senesces early.

Control: Chemical control and the use of resistant cultivars. Resistance has been documented in populations of P. fusca to some of the chemicals registered for control.
Colonic left‐side increase of eosinophils: a clue to drug‐related colitis in adults
Authors: CASELLA G. , VILLANACCI V. , FISOGNI S. , CAMBARERI A. R. , DI BELLA C. , CORAZZI N. , GORLA S. , BALDINI V. , BASSOTTI G.
Published: December 2008

Background  The colon shows frequent eosinophilic infiltration in allergic proctocolitis of infants, whereas in adults, eosinophilic infiltration of the colon is less defined and may be found in different conditions including drug‐induced colitis, even though the pathological findings are often inconsistent.

Aim  To quantify eosinophils in the mucosa of normal controls and to compare them with those of patients with abdominal symptoms related to ‘drug colitis’.

Methods  Mucosal biopsies were obtained during colonoscopy in 15 controls and in 27 patients with abdominal symptoms, a history of probable ‘drug‐related colitis’ and without obvious causes of eosinophilia.

Results  The drugs related to the patient symptoms were nonsteroidal anti‐inflammatory drugs (70%), antiplatelet agents (19%) and oestroprogestinic agents (11%). Colonoscopy was normal in 30% of patients and abnormal in 70%. Histology showed low content of inflammatory cells and normal crypt architecture in‐patients with endoscopy similar to inflammatory bowel diseases. The eosinophil score was significantly higher in the left side of the colon in the patient group compared with controls.

Conclusions  The finding of an increased eosinophil count limited to the left (descending and sigmoid) colon is an important clue towards a diagnosis of drug‐related colitis
Gold- and silver-induced murine autoimmunity – requirement for cytokines and CD28 in murine heavy metal-induced autoimmunity
Authors: Havarinasab S , Pollard K M , Hultman P
Published: December 2008

Treatment with gold in the form of aurothiomaleate, silver or mercury (Hg) in genetically susceptible mouse strains (H-2s) induces a systemic autoimmune condition characterized by anti-nuclear antibodies targeting the 34-kDa nucleolar protein fibrillarin, as well as lymphoproliferation and systemic immune-complex (IC) deposits. In this study we have examined the effect of single-gene deletions for interferon (IFN)-γ, interleukin (IL)-4, IL-6 or CD28 in B10.S (H-2s) mice on heavy metal-induced autoimmunity. Targeting of the genes for IFN-γ, IL-6 or CD28 abrogated the development of both anti-fibrillarin antibodies (AFA) and IC deposits using a modest dose of Hg (130 µg Hg/kg body weight/day). Deletion of IL-4 severely reduced the IgG1 AFA induced by all three metals, left the total IgG AFA response intact, but abrogated the Hg-induced systemic IC deposits. In conclusion, intact IFN-γ and CD28 genes are necessary for induction of AFA with all three metals and systemic IC deposits using Hg, while lack of IL-4 distinctly skews the metal-induced AFA response towards T helper type 1. In a previous study using a higher dose of Hg (415 µg Hg/kg body weight/day), IC deposits were preserved in IL-4−/− and IL-6−/− mice, and also AFA in the latter mice. Therefore, the attenuated autoimmunity following loss of IL-4 and IL-6 is dose-dependent, as higher doses of Hg are able to override the attenuation observed using lower doses.
Mast cells as regulators of adaptive immunity to tumours
Authors: Wasiuk A , De Vries V C , Hartmann K , Roers A , Noelle R J
Published: December 2008

The observation that mast cells accumulate at the periphery of growing tumours is now well documented, and the loss of mast cells correlates with reduced tumour growth. The role of mast cells as innate regulators of both inflammatory and immunosuppressive responses slowly becomes clear as novel tools become available. This review will address the role of mast cells in tumours and how they can interact with the local immune environment to mediate immune suppression contributing to tumour escape.
Giant cell formation in sarcoidosis: cell fusion or proliferation with non-division?
Authors: Van Maarsseveen T C M Th , Vos W , Van Diest P J
Published: December 2008

Granulomas are inflammatory reactions featuring macrophages, epithelioid, T and multi-nucleated giant cells (MGC). Giant cells are present in a number of granulomatous reactions, but little is known about their formation and function, especially in man. We studied MGC in the granulomatous disorder sarcoidosis. In situ labelling of lymph nodes by means of [3H]-thymidine showed that proliferation and non-division of epithelioid cells leading towards giant cells was not observed in these granulomas. However, [3H]-uridine incorporation showed MGC with labelled as well as unlabelled nuclei in the same cell, pointing to a process of fusion of epithelioid cells to form giant cells. Apoptotic bodies were incidentally found in granulomas. A novel finding was that such bodies were statistically more often found in the close vicinity of MGC, but not within these cells. These apoptotic cells appeared to be CD4+ lymphocytes or histiocytes. CD44 and CCR-5 involved in the process of fusion were expressed in MGC. In conclusion, MGC in sarcoidosis derive by cell fusion rather than by proliferation and non-division, and seem to play an active role in the induction of apoptosis in granulomas.
Effect of leptin on motility, capacitation and acrosome reaction of human spermatozoa
Authors: Li H. W. R. , Chiu P. C. N. , Cheung M. P. L. , Yeung W. S. B. , O W. S.
Published: December 2008

Leptin is a polypeptide hormone with important roles in reproduction. It has been detected in human seminal plasma as well as on human ejaculated spermatozoa. This study aimed at studying the possible role of leptin in regulating human sperm functions. Immunofluorescent staining was used to study the expression of leptin and its receptor. The correlation between the concentration of leptin and soluble leptin receptor (ObRs) in seminal plasma as measured by enzyme‐linked immunosorbant assay and sperm motility parameters measured by computer‐assisted sperm analyais (CASA) was determined. The effects of recombinant leptin on human sperm motility, capacitation and acrosome reaction as measured by chlortetracycline staing were also studied. Leptin immunoreactivity was demonstrated at the equatorial and neck regions of human spermatozoa, whereas that of ObRs was shown up on the tail. After Percoll separation, spermatozoa with high density had more intense leptin immunoreactivity compared with those with low density. No significant correlation was found between seminal plasma concentration of leptin/ObRs and sperm motility parameters. After incubation with recombinant human leptin for either 3 h or overnight, there was no change in all the CASA motility parameters determined and percentages of capacitated and acrosome‐reacted spermatozoa. We concluded that leptin does not have a significant effect on motility and capacitation/acrosome reaction in human ejaculated mature spermatozoa. Its role in male reproduction is yet to be determined.
Clinical and metabolic evaluation of subjects with erectile dysfunction: a review with a proposal flowchart
Authors: Foresta C. , Caretta N. , Corona G. , Fabbri A. , Francavilla S. , Jannini E. , Maggi M. , Bettocchi C. , Lenzi A.
Published: December 2008

Erectile function is a haemodynamic phenomenon depending on the integrity of neurological, vascular, endocrinological, tissue (corpora cavernosa), psychological and relational factors; changes in any one of these components may lead to erectile dysfunction (ED). ED and its comorbid conditions share common risk factors such as endothelial dysfunction, atherosclerosis and metabolic and hormonal abnormalities. Furthermore, although cross‐sectional studies have shown a clear age‐dependent association between ED, diabetes mellitus, hypertension, metabolic syndrome (MetS) and cardiovascular diseases, longitudinal evidence has recently emphasized that ED could be an early marker of these conditions. Recently, the European Association of Urology and American Urology Association provided consensus guidelines for the management of ED patients. However, the metabolic aspect of ED is rather neglected or not sufficiently treated. In this study, more emphasis will be placed on the presence of ED comorbid metabolic factors. The primary and secondary goals of therapy, according to current guidelines and to prevent their clinical evolution, will also be provided. We review the concepts of metabolic diseases related to ED and their treatment. Criteria for the diagnosis and treatment of hypogonadism, metabolic and vascular disease related to ED were analysed. ED can mark the starting point for the evaluation and prevention of significant severe diseases (such as diabetes, MetS, dyslipidaemia, arteriosclerosis, hypertension, ischaemic cardiopathy, neuropathy, etc.) hitherto unknown by the patients. Most widely used criteria for the diagnosis and treatment of these diseases were reported. We suggest a clinical approach which allows the identification of metabolic and others systemic pathologies contributing to the development of ED. This approach may constitute an improvement in disease prognosis and either induce a spontaneous reduction of ED or facilitate its specific therapy.
Development of the NBT assay as a marker of sperm oxidative stress
Authors: Tunc Ozlem , Thompson Jeremy , Tremellen Kelton
Published: December 2008

Oxidative stress is a well‐established cause of male infertility, with reactive oxygen species (ROS) causing infertility principally by impairing sperm motility and DNA integrity. Currently, most clinics do not test their infertile patients for the presence of oxidative stress because the available tests are expensive or difficult to perform. As antioxidant therapy may improve sperm DNA integrity and pregnancy outcomes, it has become apparent that there is an unmet clinical need for an inexpensive and easy‐to‐perform assay to identify sperm oxidative stress. The aim of this study was to develop a standardized protocol for performing a photometric nitro blue tetrazolium (NBT) assay for the measurement of seminal ROS production via production of coloured formazan, whilst correlating these results with impaired sperm function (motility and DNA integrity). Semen samples from 21 fertile and 36 male aetiology infertile men were assessed for ROS production (NBT assay), sperm DNA integrity (TUNEL), apoptosis (Annexin V) and sperm motility. Infertile men’s semen contained on average fourfold higher levels of ROS than fertile men. The production of ROS by sperm was positively correlated with sperm DNA fragmentation and apoptosis, whilst being negatively correlated with sperm motility. Receiver‐operating characteristic plot analysis established a cut‐off point of 24 μg formazan/107 sperm having a sensitivity of 91.7% and a specificity of 81% for determining the fertility status of an individual. This study has been successful in establishing a standardized protocol for performing a photometric seminal NBT assay that has significant clinical utility in identifying men with impaired fertility because of oxidative stress.
Galanin modulates vagally induced contractions in the mouse oesophagus
Authors: Boudaka A. , Wörl J. , Shiina T. , Shimizu Y. , Takewaki T. , Neuhuber W. L.
Published: December 2008

Abstract Nitrergic myenteric neurons co‐innervating motor endplates were previously shown to inhibit vagally induced contractions of striated muscle in the rodent oesophagus. Immunohistochemical demonstration of putative co‐transmitters, e.g. galanin, in enteric neurons prompted us to study a possible role of galanin in modulating vagally mediated contractions in anin vitrovagus nerve‐oesophagus preparation of the mouse. Galanin (1–16) (1–100 nmol L−1), in the presence of the peptidase inhibitor, phenanthroline monohydrate, inhibited vagally induced contractions in a concentration‐dependent manner (control: 100%; galanin 1 nmol L−1: 95.6 ± 1.6%; galanin 10 nmol L−1: 57.3 ± 6.5%; galanin 100 nmol L−1: 31.2 ± 8.1%,n = 5). The non‐selective galanin receptor antagonist, galantide (100 nmol L−1), blocked the inhibitory effect of galanin (10 nmol L−1) while the selective non‐galanin receptor 1 and galanin receptor 3 antagonists, M871 (1 μmol L−1) and SNAP37889 (100 nmol L−1), respectively, and the nitric oxide synthase inhibitor,NG‐nitro‐l‐arginine methyl ester(l‐NAME)(200 μmol L−1), failed to affect this galanin‐induced response. Simultaneous application of galantide (100 nmol L−1) andl‐NAME(200 μmol L−1) significantly reduced the inhibitory effect of capsaicin (30 μmol L−1) on vagally induced contractions when compared with its effect in the presence ofl‐NAME alone or in combination with the selective galanin receptor 2 or 3 antagonists. An inhibitory effect of piperine on vagally induced contractions was reduced neither by galantide nor byl‐NAME. Immunohistochemistry revealed galanin immunoreactive myenteric neurons and nerve fibres intermingling with cholinergic vagal terminals at motor endplates. These data suggest that galanin from co‐innervating enteric neurons co‐operates with nitric oxide in modulating vagally induced contractions in the mouse oesophagus.
Neurochemical plasticity in the enteric nervous system of a primate animal model of experimental Parkinsonism
Authors: Chaumette T. , Lebouvier T. , Aubert P. , Lardeux B. , Qin C. , Li Q. , Accary D. , Bézard E. , Bruley Des Varannes S. , Derkinderen P. , Neunlist M.
Published: December 2008

Abstract  Emerging evidences suggest that the enteric nervous system (ENS) is affected by the degenerative process in Parkinson’s disease (PD). In addition lesions in the ENS could be associated with gastrointestinal (GI) dysfunctions, in particular constipation, observed in PD. However, the precise alterations of the ENS and especially the changes in the neurochemical phenotype remain largely unknown both in PD and experimental Parkinsonism. The aim of our study was thus to characterize the neurochemical coding of the ENS in the colon of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated monkeys, a well‐characterized model of PD. In the myenteric plexus, there was a significant increase in the number of neurons per ganglia (identified with Hu), especially nitric oxide synthase immunoreactives (IR) neurons in MPTP‐treated monkeys compared to controls. A concomitant 72% decrease in the number of tyrosine hydroxylase‐IR neurons was observed in MPTP‐treated monkeys compared to controls. In contrast no change in the cholinergic or vasoactive intestinal peptide‐IR population was observed. In addition, the density of enteric glial cells was not modified in MPTP‐treated monkeys. Our results demonstrate that MPTP induces major changes in the myenteric plexus and to a lesser extent in the submucosal plexus of monkeys. They further reinforce the observation that lesions of the ENS occur in the course of PD that might be related to the GI dysfunction observed in this pathology.
A Study on HL—A System in Japanese
Authors: SAITOI S. , NAITO S. , TOYODA K. , KONOMI K. , YAMAMOTO H. , NISHIMURA M. , ARAKAWA K. , NOMOTO K.
Published: December 2008

Two hundred unrelated Japanese individuals were HL—A typed with UCLA Research Tray T3 (Terasaki's Tray), which contains specificities added after the Fifth International Workshop.

Phenotype, gene and haplotype frequencies were calculated with standard errors and delta values. HL—A9, HL—A5 and W10 had a higher frequency and HL—A1, 3 and 8 had a lower frequency in Japanese than in Caucasians. The frequent haplotypes were HL‐A9‐ HL—A5, HL—A9‐HL—A7 and HL—A2‐W10. HL—A9‐HL—A5 showed very positive high linkage disequilibrium parameter (delta value) and HL‐A9‐W10 showed negative high value. The sera designated as anti‐HL‐A, W5 and W15 in the T3 Tray which react identically in Caucasians showed different patterns of reaction when tested in the Japanese population.

Five hundred Japanese parous women's sera were tested for cytotoxic antibodies. Some Japanese antisera showed high correlation coefficient values on HL—A2, HL—A9, HL‐A10, HL‐All and HL‐A12. The women providing the anti‐HL‐5 complex sera and their immunizing persons were HL‐A typed. These complex sera reactions were compared with the antisera in the T3 Tray. A new group of sera (SN‐1), “operationally monospecific” and cross‐reacting with W22, was found in the present study. Population and family studies suggested that the sera SN‐1 are third in frequency within the second series (phenotypic frequency 17–22%) and show high delta values with HL‐All in the Japanese population.
A Simple Freezing and Storage Method to Preserve the Stimulating Function of Leukocytes in the Mixed Leukocyte Reaction
Authors: OSOBA DAVID , FALK JUDY , DAJKO MARIEKE , RICHARDSON JOHN
Published: December 2008

Human peripheral blood leukocytes retain their capacity to function as stimulating cells in the one way MLR after freezing and storage at ‐ 70° C by a simple and inexpensive method. This storage method facilitates the use of a standard stimulating pool of cells from three donors which may provide a quantitative assay for testing the ability of cells to respond to allogeneic cells in culture.
Third HL—A Segregant Series: Genetic Analysis and Molecular Independence on Lymphocyte Surface
Authors: PIERRESI M. , FRADELIZI D. , NEAUPORT‐SAUTES C. , DAUSSET J.
Published: December 2008

Five sera which detect two alleles of the third HL—A locus (T2 and T4) are described. Statistical analysis of a panel of 220 donors gave gene frequencies in a French Parsian population which are comparable to the results of Scandinavian author. Segregationabserved in 50 families emphssized thnkage disequilibirum with SD2 alleles. T1 was found to be associated woth the one part of W22 (Da30) and T3 with the other part (non‐Da30). No recombination was observed between SD2 and SD3, and the distace between these two loci can be estimated at less than distance between these two loci can be estimated at ess than 0.0042 U.

Differential capping experiments showed that redistribution of SD3 antigens did not affect the SD2 or SD1 products, indicating that they are borne on the cell surface by independent structure. Moreover, capping of SD1, SD2 and SD3 antigens did not provoke complete redistribution of beta‐2‐microglobulin which suggests that not all β2M molecules are linked to HL—A antigens.
Direct Cell Mediated Lympholysis. A Test of Allograft‐Rejection in Human Kidney Recipients
Authors: GRUNNET N. , KRISTENSEN T. , KORNERUP H. J. , KlSSMEYER‐NlELSEN F.
Published: December 2008

In kidney transplanted patients a clear coincidence was observed between clinical signs of allograft rejection and the presence in the peripheral blood of killer cells able to lyse either PHA lymphoblasts from the actual donor or selected unrelated individuals. In recipients with non‐immunological complications such as leakage on the graft ureter or primary anuria caused by renal ischaemia, no cellular cytotoxicity against specific or selected target cells was observed.

The specificity of this Cell Mediated Lympholysis in two of the cases reported could not be explained by the serologically detectable HL‐A antigens, indicating the existence of other determinants of importance for the killing capability ofin vivoproduced effector cells.
Low HL—A2 Frequency and Periodontitis1
Authors: TERASAKI PAUL I. , KASLICK RALPH S. , WEST THEODORE L. , CHASENS ABRAM I.
Published: December 2008

The frequency of HL‐A2 was significantly low (21 %) in patients with periodontitis when compared to controls who were free of periodontal disease (61 %). The effect was most pronounced in females in whom HL—A2 was present in 12.5 % (2 out of 16). This finding suggests that genes controlling susceptibility to microbial agents may be linked to the HL‐A locus.
Mixed Lymphocyte Culture Search for HLA‐D Homozygous Typing Cells in the Hungarian Inbred Population of Ivád
Authors: Ónody Clara , Kristensen Tom , Nemeskéry J. , Gyódy Eva , Bátory Gabriella , Bojárszky Katherine
Published: December 2008

Six functionally HLA‐D homozygous typing cells were identified by a restricted investigation into the Hungarian inbred population of Ivad. These putative HLA‐D homozygous typing cells were then tested against a highly selected Scandinavian population sample of 60 individuals previously typed by histocompatibility reference reagents. Three different HLA‐D specificities could thus be identified: one closely matching HLA‐Dw5, another resembling the Oslo LDoH specificity, while the last seems to be unique.

Only one of the typing cells thus ascertained were HLA‐B homozygous and were selected on the basis of the Ivád family structure and not on the basis of serological HLA typing.
Nomenclature for Factors of the HLA System‐1977
Authors: Albert E. , Amos D. B. , Bodmer W. F. , Ceppellini R. , Dausset J. , Kissmeyer‐Nielsen F. , Mayr W. , Payne Rose , van Rood J. J. , Terasaki P. I. , Trnka Z. , Walford R. L.
Published: December 2008

A nomenclature committee composed of geneticists and immunologists, including specialists in tissue typing, has met after each of the Histocompatibility Testing workshops beginning with the 3rd Workshop in 1967. The committee met again, in part under the auspices of the World Health Organisation and to report to the International Union of Immunological Societies, after the 7th workshop in Oxford in September 1977, with the aim of updating the nomenclature for specificities of the HLA—A,—B,—C and—D loci and establishing a nomenclature for the new specificities identified by serological techniques on B lymphocytes.
Primed Lymphocyte Typing (PLT): Dichotomizing Responses into “Positives” and “Negatives”
Authors: Sheehy Michael J.
Published: December 2008

In primed lymphocyte typing (PLT), it will often be useful to divide the test cells for any given reagent into a positive and a negative group. Some general problems in PLT analysis are discussed here. The author describes a model for PLT data, to provide a conceptual framework, and suggests a statistical procedure based on the model.
Bu—A New Antigen at the HLA‐B Locus
Authors: Laundy G. J. , Entwistle C. C. , Hassenkamp K.
Published: December 2008

Evidence is presented for a new allele at the HLA—B locus defining a new antigen, Bu. Population studies indicate a gene frequency of 0.0043 in English Caucasians. No HLA—B locus triplets involving the Bu antigen have been observed. Inheritance of Bu has been established in three informative families, each of at least three generations. Platelet absorption studies and analysis of a large number of multispecific HLA—B antisera suggest that Bu is “intermediate” between the well‐established antigens Bw15 and Bw21.
On the Mapping of PGM3, GLO and HLA
Authors: Lamm L. U. , Weitkamp L. R. , Jensson O. , Pedersen G. Bruun , Kissmeyer‐Nielsen F.
Published: December 2008

In a combined Danish, American and Icelandic study, the odds for the orientation PGM3:GLO:HLA‐B:HLA‐A versus GLO: HLA‐B:HLA‐A:PGM3 are estimated to be 75:1. The GLO:HLA recombination frequency is estimated at 5% for males and 12% for females. The recombination fraction for PGM3:GLO is 12–13% in males and is significantly higher in females (approximately free recombination). The findings are consistent with the large sex differences in recombination frequency between HLA and PGM3.
HLA Polymorphism in Israel: 3. Ashkenazi Jews of German Descent
Authors: Bonné‐Tamir B. , Bodmer J. G. , Modai J.
Published: December 2008

Seventy‐three random Jewish individuals whose families have lived in Germany for at least 4–5 generations, were typed for HLA antigens at the A and B loci.

In comparison with other European populations, the frequencies of B7 and B12 are low whereas Bw35 is almost twice as frequent (21%). Among the uncommon associations found in the German Jews were: (A2, Bw21), (Aw25, B18), (A29, B14), (A28, Bw15). The frequent haplotype (Aw24, Bw35) was previously found, but only in Asia and in American Indians.

Subdivisions of the subjects according to geographic regions within Germany point to differences in gene frequency between the groups.
HLA Polymorphism in Israel
Authors: Bonné‐Tamir B. , Bodmer J. G. , Modai J.
Published: December 2008

Phenotype and gene frequencies of antigens at the A and B HLA loci were determined in a sample of 89 random Libyan Jews now settled in Israel. Most antigens at the A locus are within the range found in European populations while, at the B locus, the frequencies differ from Caucasoid populations: B7 is usually rare (1%), Bw35 is frequent (14%) and Bw40 very common with more than 10%.

Thirteen percent of Libyan women whose sera were screened for the presence of HLA antibodies gave positive results. Some of them are elderly women, about 15 years or more beyond their last birth.
HLA Polymorphism in Israel
Authors: Gazit E. , Brautbar C. , Mizrachi Y. , Cohen R. , Yehoshua H. , Zamir R.
Published: December 2008

One hundred and twenty three Iraqi Jews, now living in Israel, were studied for their HLA polymorphism. Gene frequencies exceeding. 1 were found for A1, A3, Aw19, B5, B12, and Bw35. A28, B8 and B14 were relatively rare whereas Aw25 and Bw37 were not found at all. Significant gametic associations occurred for (Aw23, Bw21), (Aw26, Bw16), (A11, B5), (A28, B8) and (A28, B7). The Iraqi Jewish population was found to be typical of Asiatics and Middle Easterners.
HLA Polymorphism in Israel 8. The Armenian Community in Jerusalem
Authors: Bonné‐Tamir B. , Bodmer J. G. , Young D. , Ashbel S.
Published: December 2008

Gene and phenotype frequencies for the three HLA loci were determined for 90 random Armenians from the Old City of Jerusalem, Relatively high frequencies were found for HLA—A2, A3 and Aw24, while the lowest frequencies were those for Aw23 and Aw25. The major distinguishing antigen, when compared with European Caucasoids is Bw35 with a frequency of 22%.

Two unusual associations between the B and C loci were observed: Bw17, Cw3 and B7, Cw3. Another interesting association in Armenians, Aw32 Cw4, has previously been found only among Cochini Jews and Malay populations.
HLA Polymorphism in Israel: 9. An Overall Comparative Analysis
Authors: Bonné‐Tamir B. , Bodmer J. G. , Bodmer W. F. , Pickbourne P. , Brautbar C. , Gazit E. , Nevo S. , Zamir R.
Published: December 2008

HLA gene frequencies in 11 Israeli populations and nine other relevant populations were used to calculate genetic distances in a quantitative assessment of their similarities and differences.

The shortest distance found is between Polish and Rumanian Jews, while the largest is between Russian Jews and Black Africans. Estimates of “average” distances within major population groups suggest that the Ashkenazi Jews (Poles, Russians, Rumanians and Germans) are a more homogeneous population than East European non‐Jews or than Middle‐Eastern populations (Arabs, Armenians, Lebanese and Turks).

A cline of distances between Ashkenazi Jews and other Jewish communities parallels their geographic distribution; however, the relatively large distance between the two North African communities (Libyans and Moroccans) demonstrates that geographic proximity is not necessarily correlated with genetic similarity.

The Jewish populations, especially the Ashkenazi, show a clear divergence from their neighboring non‐Jewish populations, among whom they have lived for many centuries.

There are indications in theHLAdata of a common origin for the diverse Jewish populations.
The HLA Bw4/w6 Diallelic System in Graves' Disease
Authors: Farid Nadir R. , Barnard John M. , Noel Laura Sampson Elke P. , Marshall William H.
Published: December 2008

We studied the diallelic system HLA—Bw4/w6 in patients with Graves' disease and control subjects. Twenty‐one out of the 22 patients with Graves' disease were found to be HLA—Bw6 positive and 16 of these were homozygous, contrasted with 28 and 9 out of 34 controls, respectively. HLA—Bw6 positivity results in a relative risk for Graves' disease of 3.27; homozygosity for that allele further increases the risk to 7.4. It is possible that the increased risk attached to HLA—Bw6 is secondary to the increase in HLA—B8 previously described in Graves' disease.
Diminished Mixed Lymphocyte Response in Ankylosing Spondylitis
Authors: Wee S. L. , Daymond T. J.
Published: December 2008

A diminished mixed lymphocyte response was reported by Nikbin et at. (1976) among patients with ankylosing spondylitis, their asymptomatic relatives and also normal controls carrying the B27 antigen. In the present communication, the responses in 48 ankylosing spondylitis patients and 45 controls were examined in mixed lymphocyte cultures tested against a ‘standard stimulator’ made up of pooled lymphocytes. A significantly diminished response is confirmed among the ankylosing spondylitis patients, but not in the control group carrying the B27 antigen. The diminished mixed lymphocyte response therefore appears to be more directly associated with the disease than with the B27 antigen, and possibly represents a specific T‐cell defect associated with the pathogenesis of the disease.
HLA‐Bw54 (Bw22‐J, J‐1) Antigen in Juvenile Onset Diabetes Mellitus in Japan
Authors: Okimoto Kyoko , Juji Takeo , Ishiba Shuntaro , Maruyama Hiroshi , Tohyama Hiroshi , Kosaka Kinori
Published: December 2008

HLA—B8 and/or Bw15, associated with juvenile onset insulin‐dependent diabetes mellitus (JDM) in Caucasians, have a very low frequency in the Japanese population. Thus, we were interested in investigating the association between JDM and HLA antigen in a Japanese population. Eighty‐nine patients with JDM and 128 unrelated random controls were HLA‐typed by the micro‐lymphocytotoxicity test. The data revealed a significant, positive association between this type of diabetes mellitus and HLA‐Bw54 (Bw22‐J, J‐1) antigen (Japanese‐specific split antigen of HLA—Bw22).
HLA—D Typing in 72 Psoriasis Vulgaris Patients: Distribution of Seven HLA—D Alleles
Authors: Grosse‐Wilde H. , Wüstner H. , Albert E. D. , Kuntz B. , Scholz S. , Braun‐Falco O.
Published: December 2008

The phenotype distribution of seven HLA—D alleles among 72 unrelated Psoriasis vulgaris patients was investigated. Statistically significant deviation from the antigen frequency in healthy donors was found for a new HLA—D allele, locally designated EI, with a relative risk value of 5.97. This observation indicates that Psoriasis vulgaris belongs to the group of diseases with associations to HLA—B as well as HLA—D alleles.
HLA—B27 Homozygosity in Ankylosing Spondylitis: Relationship to Risk and Severity
Authors: Khan M. A. , Kushner I. , Braun W. E. , Zachary A. A. , Steinberg A. G.
Published: December 2008

The observed frequency of apparent homozygotes for HLA—B27 (15.5%) was significantly greater than the estimated expected frequency (4.2%) among 58 B27‐positive Caucasian patients with ankylosing spondylitis (AS) (P < 0.0005). Search of the literature uncovered four other studies in each of which the frequency of apparent homozygotes was shown by our analysis to be greater than expected. These analyses indicated that B27 homozygotes are more susceptible to developing AS than are B27 heterozygotes. Comparison of the clinical features of AS showed no differences between heterozygotes and apparent homozygotes except for a higher frequency of involvement of peripheral joints in the latter group.
Low Responsiveness in MLC Induced by Certain HLA—A Antigens on the Stimulator Cells
Authors: Thomsen M. , Dickmeiss E. , Jakobsen B. K. , Platz P. , Ryder L. P. , Svejgaard A.
Published: December 2008

An individual, BK, repeatedly gave typing responses against homozygous typing cells representing more than two HLA—D antigens. Family studies showed that she had inherited the HLA—Dw2 and Dw7 determinants, in agreement with results from primed lymphocyte typing. The HLA—A, B, C types of the stimulators giving rise to unexpected typing responses all involved the HLA—A1, A3 or A11 antigens. The hypothesis of this specificity in low‐responsiveness was confirmed in the independent stimulator sample provided by the 7th workshop homozygous typing cell panel. The same pattern was observed when BK was tested as a responder towards related and unrelated heterozygous stimulators.

Furthermore, in three‐cell experiments it was found that BK cells were able to suppress the response to the Dw‐identical individual, BS, towards stimulators carrying HLA—A1, A3, or A11. This effect of BK's cells appeared to be radiosensitive. We were not able to demonstrate suppressive supernatant factors in the relevant cultures, neither were we able to find circulating cytotoxic cells by the direct CML‐technique, nor an accelerated cytotoxic response by the indirect CML‐technique against targets carrying HLA—A1 or A3. This is the first demonstration of induction of suppressor cells in MLC by HLA—A, B, C antigens in the stimulator cells.
Proliferative Response of H‐2 Incompatible Leukocytes to an Abelson Virus‐Induced Lymphoma Cell Line Apparently Not Expressing Ia‐Antigens
Authors: Collavo Dino , Rijnbeek Annemarie , Nabholz Markus
Published: December 2008

The proliferative response of normal lymph node cells from different mouse strains to an Abelson virus‐induced leukemic cell line (MLVA) in mixed leukocyte culture (MLC) has been investigated. MLVA leukemic cells do stimulate a specific response and the stimulating determinants are controlled, most likely, by genes in the K‐end of the H—2 complex. However, using two different anti‐la sera and different assay systems, we were unable to detect the expression of Ia‐antigens on MLVA. In addition, an alloantiserum raised against MLVA, and absorbed with P815, a non‐stimulating mastocytoma cell line, showed no residual activity against MLVA cells.
Studies of the HLA Complex in Families of Children with Congenital Heart Disease
Authors: Friedman J. M. , Paul M. H.
Published: December 2008

In order to test the hypothesis that HLA‐linked developmental determinants are involved in the pathogenesis of congenital heart disease, we performed tissue typing on 10 families in which two or more siblings had cardiac malformations. No association between the occurrence of congenital heart disease and the HLA complex was found.
Transplantation in Miniature Swine. III: Effects of MSLA and A‐O Blood Group Matching on Skin Allograft Survival
Authors: Leight George S. , Kirkman Robert , Rasmusen Benjamin A. , Rosenberg Steven A. , Sachs David H. , Terrill Richard , Williams G. Melville
Published: December 2008

The fate of split thickness skin allografts between and among major histocompatibility complex (MSLA) homozygous herds of miniature swine has been examined. Among animals matched for all known blood groups, MSLA‐identical skin grafts survived 11.8 ± 0.89 days, while skin grafts from animals differing for one or two haplotypes survived 7.0 ± 0.36 days. Cytotoxic antibodies invariably appeared in the serum of animals rejecting MSLA‐nonidentical grafts, and were never detected among animals rejecting MSLA‐identical grafts.

Among the homozygous DD herd, it was possible to assess the effect on skin allograft survival of a defined difference at the A‐O blood group locus. Skin grafts between DD animals identical at the A‐O blood group locus. Skin grafts between DD animals differing at this locus survived 7.66 ± 0.54 days. Blood group O animals rejecting skin from blood group A animals produced a low liter of antibodies which were cytotoxic for donor lymphocytes. These antibodies were at least partially absorbable by donor red cells. An absorption analysis using other blood group‐defined animals of these herds showed that ability to absorb activity segregated with the A blood group.

These studies confirm the expectation that MSLA is a major histocompatibility complex of miniature swine, having important implications for the outcome of allografts. In addition, they show that the A‐O blood group, or a locus closely linked to it, is also a histocompatibility locus in pigs, and must be respected in allografting studies.
Cell Surface Antigens Detected on Mature and Leukemic Granulocytic Populations by Cytotoxicity Testing
Authors: Drew S. I. , Carter B. M. , Terasaki P. I. , Naiem F. , Nathanson D. S. , Abromowitz B. , Gale R. P.
Published: December 2008

Using a microcytotoxicity assay, the serological reactivity of human granulocytes, namely neutrophils and eosinophils, and chronic myeloid leukemia (CML) cells and cultured CML cell lines (K562, NALM‐1) were examined. Mature granulocyte forms and cord granulocytes are readily lysed by specific granulocyte cytotoxins that do not react with random T and B lymphocytes, monocytes, red blood cells, or platelets. Furthermore, certain antisera were preferentially cytotoxic for eosinophil‐enriched populations. Granulocytotoxins detected antigens on one of three CML blast cell populations tested and K562, but failed to react with NALM‐1. By cytotoxicity, mature granulocytes were poor targets for B2‐microglobulin and the appropriate HLA antisera although both sera types are absorbed with granulocytes. Furthermore, granulocytes did not possess B‐lymphocytes (la‐like) or blood group A, B, and Rh (D) antigens. Except for K562, both HLA and heterologous B‐lymphocyte antisera were cytotoxic for the CML blast cell populations tested.
The Affected Sib Pair IBD Distribution for HLA‐Linked Disease Susceptibility Genes
Authors: Suarez Brian K.
Published: December 2008

The distribution of identity by descent (IBD) scores for sib pairs affected with a disease determined by a disease susceptibility (DS) locus tightly linked to the HLA complex is derived. It is shown that the sib pair IBD distribution differs from its a priori distribution and, moreover, is completely specified by three observable population parameters‐the additive and dominance variances and the prevalence of the disease in the population. An application of the model is illustrated using data on juvenile diabetes mellitus.
HLA‐A,‐B,‐C and‐D Antigens in Male Patients with Myasthenia Gravis
Authors: Säfwenberg J. , Hammarström L. , Lindblom J. B. , Matell G. , Möller E. , Osterman P. O. , Smith C. I. E.
Published: December 2008

HLA‐A,‐B,‐C and‐D antigens were determined in 54 male Myasthenia Gravis patients. A significant increase of the B8 antigen frequency was found among patients with an onset of the disease before the age of 35. No significant increase was found among the D antigens. In a combined male and female material with an early age at onset, thymic hyperplasia was correlated to the presence of HLA‐B8.