Donor KIR2DL1 Allelic Polymorphism Influences Posthematopoietic Progenitor Cell Transplantation Outcomes in the T Cell Depleted and Reduced Intensity Conditioning Setting.

The majority of established KIR clinical assessment algorithms used for donor selection for hematopoietic progenitor cell transplantation (HPCT) evaluate gene content (presence/absence) of the KIR gene complex. In comparison, relatively little is known about the impact of KIR allelic polymorphism. By analyzing donors of T cell depleted (TcD) reduced intensity conditioning (RIC) HPCT, this study investigated the influence on post-transplant outcome of 2 polymorphic residues of the inhibitory KIR2DL1. The aim of this study was to expand upon existing research into the influence of KIR2DL1 allelic polymorphism upon post-transplant outcome. The effects of allele groups upon transplant outcomes were investigated within a patient cohort using a defined treatment protocol of RIC with TcD. Using phylogenetic data, KIR2DL1 allelic polymorphism was categorized into groups on the basis of variation within codons 114 and 245 (positive or negative for the following groups: KIR2DL1*002/001g, KIR2DL1*003, KIR2DL1*004g) and the identification of null alleles. The influence of these KIR2DL1 allele groups in hematopoietic progenitor cell transplantation (HPCT) donors was assessed in the post-transplant data of 86 acute myelogenous leukemia patients receiving RIC TcD HPCT at a single center. KIR2DL1 allele groups in the donor significantly impacted upon 5-year post-transplant outcomes in RIC TcD HPCT. Donor KIR2DL1*003 presented the greatest influence upon post-transplant outcomes, with KIR2DL1*003 positive donors severely reducing 5-year post-transplant overall survival (OS) compared to those receiving a transplant from a KIR2DL1*003 negative donor (KIR2DL1*003 pos versus neg: 27.0% versus 60.0%, P = .008, pc = 0.024) and disease-free survival (DFS) (KIR2DL1*003 pos versus neg: 23.5% versus 60.0%, P = .004, pc = 0.012), and increasing 5-year relapse incidence (KIR2DL1*003 pos versus neg: 63.9% versus 27.2%, P = .009, pc = 0.027). KIR2DL1*003 homozygous and KIR2DL1*003 heterozygous grafts did not present significantly different post-transplant outcomes. Donors possessing the KIR2DL1*002/001 allele group were found to significantly improve post-transplant outcomes, with donors positive for the KIR2DL1*004 allele group presenting a trend towards improvement. KIR2DL1*002/001 allele group (KIR2DL1*002/001g) positive donors improved 5-year OS (KIR2DL1*002/001g pos versus neg: 56.4% versus 27.2%, P = .009, pc = 0.024) and DFS (KIR2DL1*002/001g pos versus neg: 53.8% versus 25.5%, P = .018, pc = 0.036). KIR2DL1*004 allele group (KIR2DL1*004g) positive donors trended towards improving 5-year OS (KIR2DL1*004g pos versus neg: 53.3% versus 35.5%, P = .097, pc = 0.097) and DFS (KIR2DL1*004g pos versus neg: 50.0% versus 33.9%, P = .121, pc = 0.121), and reducing relapse incidence (KIR2DL1*004g pos versus neg: 33.1% versus 54.0%, P = .079, pc = 0.152). The presented findings suggest donor selection algorithms for TcD RIC HPCT should consider avoiding KIR2DL1*003 positive donors, where possible, and contributes to the mounting evidence that KIR assessment in donor selection algorithms should reflect the conditioning regime protocol used.

Predicting flow cytometry crossmatch results from single-antigen bead testing.

The aim of this study was to devise an algorithm that would predict flow cytometry crossmatch (FCXM) results using single-antigen bead (SAB) mean fluorescent intensity (MFI) levels using samples received through the National External Quality Assurance Scheme (NEQAS) 2B external proficiency testing scheme between 2019 and 2023. A total of 159 serum samples were retrospectively screened using LABScreen Single Antigen Class I and II (SAB), and 40 peripheral blood samples were human leucocyte antigen (HLA) typed with LABType SSO. Donor-specific antibodies were identified for each cell-serum combination tested, and cumulative MFI values were calculated for each test before correlating the screening result with the consensus crossmatch results for this scheme. HLA Class I MFIs were combined to predict the T cell crossmatch. For the B cell crossmatch prediction, two options were considered: (i) HLA Class II MFI values alone and (ii) HLA Class I + Class II MFIs. Receiver operating characteristic analysis was carried out to identify the combined MFI threshold that predicted NEQAS consensus results with the greatest sensitivity and specificity. HLA Class I combined MFI >5000 predicted T cell crossmatch results with 96% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 92% negative predictive value (NPV). For B cell results, HLA Class I + Class II combined MFIs >11,000 gave the best model, showing 97% sensitivity, 82% specificity, 96% PPV and 85% NPV. However, for samples with only HLA Class II sensitization, combined MFIs >13,000 improved the B cell crossmatch predictions: 92% sensitivity, 95% specificity, 96% PPV and 91% NPV. Using this model, combined MFI can be used to predict the immunological risk posed by donor-specific antibodies when it is not possible to carry out an FCXM.

Wild lime psyllid Leuronota fagarae Burckhardt (Hemiptera: Psylloidea) picorna-like virus full genome annotation and classification.

Picorna-like viruses of the order Picornavirales are a poorly defined group of positive-sense, single-stranded RNA viruses that include numerous pathogens known to infect plants, animals, and insects. A new picorna-like viral species was isolated from the wild lime psyllid (WLP), Leuronota fagarae, in the state of Florida, USA, and labelled: Leuronota fagarae picorna-like virus isolate FL (LfPLV-FL). The virus was found to have homology to a picorna-like virus identified in the Asian Citrus Psyllid (ACP), Diaphorina citri, collected in the state of Florida. Computational analysis of RNA extracts from WLP adult heads identified a 10,006-nucleotide sequence encoding a 2,942 amino acid polyprotein with similar functional domain structure to polyproteins of both Dicistroviridae and Iflaviridae. Sequence comparisons of nucleic acid and amino acid translations of the conserved RNA-dependent RNA polymerase, along with the entire N-terminal nonstructural coding region, provided insight into an evolutionary relationship of LfPLV-FL to insect-infecting iflaviruses. Viruses belonging to the family Iflaviridae encode a polyprotein of around 3000 amino acids in length that is processed post-translationally to produce components necessary for replication. The classification of a novel picorna-like virus in L. fagarae, with evolutionary characteristics similar to picorna-like viruses infecting Bactericera cockerelli and D. citri, provides an opportunity to examine virus host specificity, as well as identify critical components of the virus' genome required for successful transmission, infection, and replication. This bioinformatic classification allows for further insight into a novel virus species, and aids in the research of a closely related virus of the invasive psyllid, D. citri, a major pest of Floridian citriculture. The potential use of viral pathogens as expression vectors to manage the spread D. citri is an area that requires additional research; however, it may bring forth an effective control strategy to reduce the transmission of Candidatus Liberibacter asiaticus (CLas), the causative agent of Huanglongbing (HLB).

HLA-C expression level in both unstimulated and stimulated human umbilical vein endothelial cells is defined by allotype.

Human leukocyte antigens (HLA) are present on the surface of all nucleated cells, with the level of expression dependent on the particular HLA locus, the cell type and cellular activation state. Human umbilical vein endothelial cells (HUVECs) are easily isolated from umbilical cords and may aid our understanding of HLA expression on the vascular endothelium in the setting of transplantation. Endothelial cells on the donor-recipient interface form the barrier between transplanted organs and the host immune system. Increased knowledge of the variation in levels of individual HLA specificities may inform the assessment of transplant risk. HUVECs from 48 full term babies born consecutively following planned caesarean section were isolated, HLA typed and grown on gelatin coated culture wells. Once confluent, cells were stimulated with optimal concentrations of the cytokines TNF-α and IFN-γ for 24 hours and HLA-C expression on both unstimulated and stimulated cells was quantified by flow cytometry using the fluorescent labelled monoclonal antibody DT-9 PE. Unstimulated HLA-C expression varied by over 60% between allotypes (ANOVA, P = .004). Following stimulation, HLA-C levels increased over 15-fold and showed the same variation of expression between allotypes (P < .001). Cell surface HLA-C expression increases between 500% and 3125%, after stimulation for 24 hours. HLA-C level varies between allotypes and cells expressing more HLA-C at baseline tended to have corresponding higher levels of HLA-C following cytokine stimulation (Pearson's correlation coefficient between unstimulated and stimulated expression, P = .002).

HLA expression levels of unstimulated and cytokine stimulated human umbilical vein endothelial cells.

Transplant rejection occurs following recipient recognition of mismatched HLA on donor tissue, but active rejection is dependent not only upon the severity of the T cell or alloantibody response, but also upon the cell surface expression of target HLA molecules. To investigate the variation in HLA expression using a model of endothelium, human umbilical vein endothelial cell (HUVEC) cultures were generated from 48 umbilical cords donated consecutively following planned caesarean section. HUVECs were stimulated using the cytokines tumour necrosis factor alpha and interferon gamma and HLA expression of unstimulated and stimulated cells determined using flow cytometry. HLA-A2, HLA-A3 and HLA-C antigens all showed a modest increase in expression for 12 hours post cell activation, followed by a more pronounced response over the next 24 to 36 hours. Each of these antigens increased by up to 40 times over unstimulated levels and in addition cells homozygous for specific HLA antigens on average had twice the amount of antigen expressed compared with cells heterozygous for that antigen, both when unstimulated and following cytokine stimulation. Cell activation is an important consideration in the assessment of transplant risk and may help progress towards understanding why rejection does not always occur in the presence of significant donor specific antibody. This data also confirms guidelines for transplantation, which recommend doubling the specific antibody level when considering immunological risk for homozygous donors.

Identification and Distribution of Haplotypes of Diaphorina citri (Hemiptera: Liviidae) in Jamaica and the Caribbean.

Diaphorina citri Kuwayama (Hemiptera: Psyllidae), also known as the Asian citrus psyllid, is a vector of the citrus huanglongbing (HLB) disease. D. citri transmits all three known strains of the HLB pathogen: Candidatus Liberibacter africanus, Candidatus Liberibacter americanus, and Candidatus Liberibacter asiaticus. The study involved 92 psyllids representing the Caribbean Basin and reference samples representing countries within Asia, North America, and South America. This study was aimed at characterizing D. citri on a molecular level in order to determine the haplotype diversity and uniqueness within Jamaica and the Caribbean Basin. D. citri-specific primers were used to amplify an 821 bp gene fragment from the mitochondrial cytochrome c oxidase subunit I gene (mtCOI). The statistical parsimony program, TCS, was used to determine the 12 haplotypes found within the Caribbean, with haplotypes H2 and H7 being the most prominent. The H2 haplotype was found to belong to the South Western Asia group originating from India. H2 represented 54% of the sequenced samples and dominated the Greater Antilles, 22% were grouped as H7, dominating the Lesser Antilles, while the remaining 24% of the sequences were grouped in the remaining 10 haplotypes and were variants seen within the Greater and Lesser Antilles.

A LATS biosensor screen identifies VEGFR as a regulator of the Hippo pathway in angiogenesis.

The Hippo pathway is a central regulator of tissue development and homeostasis, and has been reported to have a role during vascular development. Here we develop a bioluminescence-based biosensor that monitors the activity of the Hippo core component LATS kinase. Using this biosensor and a library of small molecule kinase inhibitors, we perform a screen for kinases modulating LATS activity and identify VEGFR as an upstream regulator of the Hippo pathway. We find that VEGFR activation by VEGF triggers PI3K/MAPK signaling, which subsequently inhibits LATS and activates the Hippo effectors YAP and TAZ. We further show that the Hippo pathway is a critical mediator of VEGF-induced angiogenesis and tumor vasculogenic mimicry. Thus, our work offers a biosensor tool for the study of the Hippo pathway and suggests a role for Hippo signaling in regulating blood vessel formation in physiological and pathological settings.

High quality clinical grade human embryonic stem cell lines derived from fresh discarded embryos.

BACKGROUND: Human embryonic stem cells (hESCs) hold tremendous promise for cell replacement therapies for a range of degenerative diseases. In order to provide cost-effective treatments affordable by public health systems, HLA-matched allogeneic tissue banks of the highest quality clinical-grade hESCs will be required. However only a small number of existing hESC lines are suitable for clinical use; they are limited by moral and ethical concerns and none of them apply Good Manufacturing Practice (GMP) standards to the earliest and critical stages of gamete and embryo procurement. We thus aimed to derive new clinical grade hESC lines of highest quality from fresh surplus GMP grade human embryos. METHODS: A comprehensive screen was performed for suitable combinations of culture media with supporting feeder cells or feeder-free matrix, at different stages, to support expansion of the inner cell mass and to establish new hESC lines. RESULTS: We developed a novel two-step and sequential media system of clinical-grade hESC derivation and successfully generated seven new hESC lines of widely varying HLA type, carefully screened for genetic health, from human embryos donated under the highest ethical and moral standards under an integrated GMP system which extends from hESC banking all the way back to gamete and embryo procurement. CONCLUSIONS: The present study, for the first time, reports the successful derivation of highest-quality clinical-grade hESC lines from fresh poor-quality surplus human embryos generated in a GMP-grade IVF laboratory. The availability of hESC lines of this status represents an important step towards more widespread application of regenerative medicine therapies.

Brain Structural and Vascular Anatomy Is Altered in Offspring of Pre-Eclamptic Pregnancies: A Pilot Study.

BACKGROUND AND PURPOSE: Pre-eclampsia is a serious clinical gestational disorder occurring in 3%-5% of all human pregnancies and characterized by endothelial dysfunction and vascular complications. Offspring born of pre-eclamptic pregnancies are reported to exhibit deficits in cognitive function, higher incidence of depression, and increased susceptibility to stroke. However, no brain imaging reports exist on these offspring. We aimed to assess brain structural and vascular anatomy in 7- to 10-year-old offspring of pre-eclamptic pregnancies compared with matched controls. MATERIALS AND METHODS: Offspring of pre-eclamptic pregnancies and matched controls (n = 10 per group) were recruited from an established longitudinal cohort examining the effects of pre-eclampsia. Children underwent MR imaging to identify brain structural and vascular anatomic differences. Maternal plasma samples collected at birth were assayed for angiogenic factors by enzyme-linked immunosorbent assay. RESULTS: Offspring of pre-eclamptic pregnancies exhibited enlarged brain regional volumes of the cerebellum, temporal lobe, brain stem, and right and left amygdalae. These offspring displayed reduced cerebral vessel radii in the occipital and parietal lobes. Enzyme-linked immunosorbent assay analysis revealed underexpression of the placental growth factor among the maternal plasma samples from women who experienced pre-eclampsia. CONCLUSIONS: This study is the first to report brain structural and vascular anatomic alterations in the population of offspring of pre-eclamptic pregnancies. Brain structural alterations shared similarities with those seen in autism. Vascular alterations may have preceded these structural alterations. This pilot study requires further validation with a larger population to provide stronger estimates of brain structural and vascular outcomes among the offspring of pre-eclamptic pregnancies.

A linkage and association analysis study in the multidrug resistance gene 1 (mdr1) in renal patients.

Several investigations demonstrated that the polymorphisms of multidrug resistance gene (MDR1) gene contribute to interindividual variability in bioavailability and tissue distribution of its substrates. Genotyping of closely spaced single-nucleotide polymorphism (SNP) markers frequently yields highly correlated data, owing to extensive linkage disequilibrium (LD) between markers. The product of multidrug resistance gene (P-gp) is an important molecule, which regulating the bioavailability of many drugs, including calcineurin inhibitors. It also reported that some MDR1 gene polymorphisms (such as 3435C>T) was associated with significantly reduced intestinal P-gp expression in T/T homozygotes. The aim of this study is to develop genotyping assays for polymorphisms of the MDR1 gene, which are believed to have functional properties and to assess the distribution of variant alleles in renal patients (UK Caucasoid). A total of ten polymorphisms in the MDR-1 gene were selected for analysis. Haplotype assays were performed by using EH programme in 172 individuals. The following possible haplotype was apparent (G-41, C-145, C-129, C+139, C+1236, G+2677, G+2956, C+3435, C+4030 and A+4036). This finding suggests the importance of haplotype assignment for the MDR1 gene.

Disentangling the role of the tau gene locus in sporadic tauopathies.

Fibrillar aggregates of abnormally hyperphosphorylated tau protein are the major component of the pathological entities, including intraneuronal neurofibrillary tangles that define the broad class of late-onset neurodegenerative disorders called the tauopathies. Mutations in the tau gene (MAPT) causing familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) confirm that tau protein dysfunction could be a primary cause of neuronal loss. However, in the sporadic tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) where MAPT mutation is absent, common variation in MAPT that defines the H1 and H2 haplotype clades strongly influences disease risk. Surprisingly, this influence on risk extends to sporadic Parkinson's disease (PD), traditionally not defined as a tauopathy. This review will focus on recent work aimed at elucidating the mechanistic basis of this haplotype-specific effect on disease risk, implicating elevated levels of MAPT expression, particularly via increased transcription and/or alterations in splicing. This conforms to an emerging picture of a shared mechanism that underlies the fundamental process(es) leading to neuronal death. Increased availability of the fibrillogenic protein substrates of the pathological aggregates that define several neurodegenerative proteopathies, eg α-synuclein in PD, ß-amyloid in AD and tau in the tauopathies, contributes to causation and risk in the familial and sporadic forms of these disorders, respectively.

Serum total homocysteine concentrations in children and adolescents in Jos, Nigeria.

BACKGROUND: Although the elevation of circulating total serum homocysteine (tHcy) concentration in a fasting state is associated with an increased risk of occlusive vascular disease in adults, the levels in children in Nigeria are not known. AIM: The goals of this study were to describe the distribution of tHcy among a representative sample of children and adolescents in Jos, Nigeria, and to test for differences in tHcy among sex and age categories. METHODS: The sampling scheme, which included persons aged 10 to 19 years, was a stratified, multistage probability design. This cross sectional study involved 182 school children drawn from secondary schools in Jos, Nigeria between January and July 2003. Fasting venous samples were collected and assayed for tHcy, Total protein and Albumin. Anthropometric measurements were taken. RESULT: The mean tHcy concentrations were 2.7 +/- 2.4 (95% CI 2.4-2.9), 3.5 +/- 3.2 (3.3-3.8) and 3.6 +/- 3.2 (3.3-4.1), 4.1 +/- 3.6 (4.0-4.4) micromol/l for the girls and boys aged 10-14 and 15-19 years, respectively. Albumin levels correlate positively with plasma total homocysteine, tHcy (r = 0.45, P = 0.03). CONCLUSION: This study provided age-specific data regarding tHcy concentrations between 10-19 years population in Jos, Nigeria. The tHcy concentration increased as a function of age in both sexes.

Polymorphisms of TLR4 but not CD14 are associated with a decreased risk of aggressive periodontitis.

OBJECTIVE: To study whether there is an association between the frequency of functional polymorphisms in the toll-like receptor 4 (TLR4) and cluster differentiation 14 (CD14) genes and periodontitis. METHODOLOGY: Genotyping for the TLR4 single-nucleotide polymorphisms (SNPs) Asp299Gly, Thr399Ile and the CD14 SNPs -159 and -1359 was completed for subjects with periodontal disease compared with control subjects. Two disease populations were investigated: 73 subjects with aggressive periodontitis (AgP; 28 males, 45 females) and 95 males with chronic periodontitis (CP). The TLR4 and CD14 polymorphisms were determined using SNaPshot primer extension with capillary electrophoresis. Comparison of allele and genotype frequencies for each polymorphism was by Fisher's exact test or chi2 analysis. RESULTS: The TLR4 Asp299Gly genotype was present in a significantly (p=0.026) lower proportion of AgP subjects (5.5%) compared with control subjects (16.3%). The unadjusted odds ratio for the Asp299Gly genotype to be associated with AgP was 0.30, 95% confidence interval 0.10-0.91. No differences were found in the prevalence of the TLR4 Asp299Gly genotype in men with CP (18.9%) compared with an age-matched control group with no evidence of periodontitis (17%). In addition, there was no difference in the distribution of the CD14 polymorphisms in either the AgP or CP populations studied compared with controls. CONCLUSION: It is concluded that in West European Caucasians, the Asp299Gly TLR4 gene polymorphism is associated with a decreased risk of AgP but not CP. Promoter polymorphisms of the CD14 gene, however, did not influence susceptibility to inflammatory periodontitis in the population cohorts studied.

Are Australian children iodine deficient? Results of the Australian National Iodine Nutrition Study.

OBJECTIVE: To document the population iodine nutritional status in Australian schoolchildren. DESIGN AND SETTING: Cross-sectional survey of schoolchildren aged 8-10 years, based on a one-stage random cluster sample drawn from all Year 4 school classes in government and non-government schools in the five mainland Australian states of New South Wales, Victoria, South Australia, Western Australia and Queensland. The study was conducted between July 2003 and December 2004. PARTICIPANTS: 1709 students from 88 schools (881 boys and 828 girls), representing 85% of the estimated target number of students. The class participation rate was 65%. MAIN OUTCOME MEASURES: (i) Urinary iodine excretion (UIE) levels (compared with the criteria for the severity of iodine deficiency of the World Health Organization/International Council for the Control of Iodine Deficiency Disorders: iodine replete, UIE > or = 100 microg/L; mild iodine deficiency, UIE 50-99 microg/L; moderate iodine deficiency, UIE 20-49 microg/L; severe iodine deficiency, UIE < 20 microg/L); (ii) Thyroid volumes measured by ultrasound (compared with new international reference values). RESULTS: Overall, children in mainland Australia are borderline iodine deficient, with a national median UIE of 104 microg/L. On a state basis, NSW and Victorian children are mildly iodine deficient, with median UIE levels of 89 microg/L and 73.5 microg/L, respectively. South Australian children are borderline iodine deficient, with a median UIE of 101 microg/L. Both Queensland and Western Australian children are iodine sufficient, with median UIE levels of 136.5 microg/L and 142.5 microg/L, respectively. Thyroid volumes in Australian schoolchildren are marginally increased compared with international normative data obtained from children living in iodine sufficient countries. There was no significant association between UIE and thyroid volume. CONCLUSION: Our results confirm the existence of inadequate iodine intake in the Australian population, and we call for the urgent implementation of mandatory iodisation of all edible salt in Australia.

Can gold therapy be used more safely in rheumatoid arthritis? Adverse drug reactions are more likely in patients with nodular disease, independent of HLA-DR3 status.

OBJECTIVE: . To investigate whether features associated with severe rheumatoid arthritis (RA) are predictive of adverse drug reactions (ADR) to gold salts, independent of HLA-DR3 status. METHODS: A cohort of patients with RA (n = 41) who developed thrombocytopenia (platelets < 100 10(6)/l) or proteinuria (> 1.0 g/24 h) upon treatment with gold sodium thiomalate was identified from patient records and matched for age, sex, and disease duration with 41 RA controls treated with gold without development of ADR. A second group of 161 random RA patients that had received gold therapy for at least as long without development of an ADR was also compared. All patients were typed for HLA-DRB1, and the presence of rheumatoid factor (RF), antinuclear antibodies (ANA), and nodules before initiation of therapy was recorded. Association of clinical or genetic factors with ADR was investigated using the McNemar test and logistic regression analysis. RESULTS: Patients with ADR were more likely to have nodular disease than their matched controls (51.3% vs 25.6%; odds ratio, OR = 3.0, p = 0.02) and more likely to be HLA-DR3 positive (41.2% vs 17.6%; OR = 3.0, p = 0.045). No difference between the groups was found for RF or ANA. Nodular disease was associated with development of ADR independently of HLA-DR3, although a combination of both factors significantly increased the likelihood of an ADR. CONCLUSION: Our data suggest that nodular disease may be a predictor of gold-induced ADR independent of HLA-DR3.

Association of symptomatic acute human parvovirus B19 infection with human leukocyte antigen class I and II alleles.

To determine the effect of the major histocompatibility complex on the development of symptoms during acute human parvovirus B19 infection, we compared human leukocyte antigen (HLA) class I and II alleles in 36 patients with symptomatic acute B19 infection with those in >900 control subjects from northwestern England. The frequency of each of HLA-DRB1*01 (P=.016), DRB1*04 (P=.007), and DRB1*07 (P<.0001) alleles was significantly higher in parvovirus B19 patients than in control subjects. In the parvovirus group, 63.9% carried the rheumatoid arthritis-associated shared epitope sequence, compared with 45% of control subjects (odds ratio [OR], 2.2; 95% confidence interval [CI], 0.97-4.8; P=.04), and carriage was associated with fatigue during the acute phase (OR, 4.2; 95% CI, 0.8-23.9; P=.047). All symptomatic parvovirus-associated HLA-DRB1 molecules carry a neutrally charged glutamine at position 10 and a positively charged lysine at position 12 of the first hypervariable region. HLA-B49 was associated with parvovirus infection independently of HLA-DRB1*01, DRB1*04, and DRB1*07.

Successful in-vitro fertilization pregnancy with spermatozoa from a patient with Kartagener's syndrome: case report.

This paper reports on the successful treatment by in-vitro fertilization (IVF) of a couple in whom the male partner had Kartagener's syndrome. His spermatozoa were severely asthenozoospermic with deficient dynein arms and disordered microtubular configuration. On computer-assisted sperm analysis (CASA) motile spermatozoa displayed straight non-progressive motility with minimal amplitude of lateral head displacement and none were hyperactivated. This is the first case report in which spermatozoa with axonemal disruption in a man with immotile cilia syndrome (ICS) have been shown to be able to penetrate the zona pellucida and fertilize oocytes. IVF may be a suitable treatment for certain variants of ICS.