Immunogenicity of meningococcal ACYW135 polysaccharide vaccine in Saudi children 5 to 9 years of age

Meningococcal tetravalent polysaccharide vaccines were observed to be immunogenic in Saudi children 5 to 9 years of age, with >90% having serum bactericidal antibody titers of > or = 8 for serogroups A, Y, and W135; for serogroup C, 77% were putatively protected after vaccination.     

Carbonic anhydrase gene expression in CA II-deficient (Car2−/−) and CA IX-deficient (Car9−/−) mice

Using real-time PCR and immunohistochemistry, we have examined the expression of carbonic anhydrase isozymes (CA) I, II, III, IV, IX, XII, XIII and XIV in the brain, kidney, stomach and colon of the wild-type, CA II-deficient ( Car2^−/− ), and CA IX deficient ( Car9^−/− ) mice. The expression of Car4, Car12, Car13 and Car14 mRNAs did not show any significant deviations between the three groups of mice, whereas both groups of CA deficient mice showed decreased expression levels of Car1 in the colon and Car3 in the kidney. The Car2 mRNA level was greatly reduced but not completely abolished in all four tissues from the Car2^−/− mice in which no CA II protein was expressed. Sequencing the Car2 cDNA isolated from C57BL6 Car2^−/− mice revealed two nucleotide differences from the wild-type C57BL6 mice. One is a silent polymorphism found in Car2 mRNA from wild-type DBA mice, which is the strain that provided the original mutagenized chromosome. The second change is a mutation that causes prematurely terminated translation at codon 155 (Gln155X). Car9 mRNA and CA IX protein expression levels were up-regulated about 2.5- and 3.6-fold, respectively, in the stomach of the Car2^−/− mice. These results suggest that the loss of function of cytosolic CA II in the stomach of Car2^−/− mice leads to up-regulation of an extracellular CA, namely CA IX, which is expressed on the cell surface of the gastric epithelium.     

The location of tick salivary antigens, complement and immunoglobulin in the skin of guinea-pigs infested with Dermacentor andersoni larvae.

Using indirect immunoflorescence techniques, tick salivary gland antigens (SGA) were demonstrable in cement deposited on the skin by ticks and in all layers of the epidermis of infested guinea-pigs close to the sites where ticks attached. The antigen remained in these sites for several days after ticks had detached. In tick-resistant but not in normal guinea-pigs, SGA, complement and IgG were deposited at the dermo-epidermal junction even at some distance from the attachment site. Complement was also demonstrable in epidermal vesicles which developed beneath larvae attached to resistant guinea-pigs. It is suggested that antigen-antibody reaction and complement activation at these sites may play a role in the development of skin lesions and the attraction of basophils to these areas in challenged tick-resistant guinea-pigs. Tick antigens were also found to be associated with dendritic suprabasal cells in the epidermis of resistant guinea-pigs. It has previously been proposed that such SGA-trapping cells are Langerhans cells. These cells, in the presence of specific antibody and complement, could also initiate epidermal lesions in resistant guinea-pigs.     

Consanguinity-associated kidney diseases in Lebanon: an epidemiological study

Consanguineous marriages are common in many countries of the Middle East including Lebanon. Their impact on the repartition of kidney diseases and on the risk for familial nephritis is not known. We surveyed all of the dialysis centers in Lebanon. Nine hundred and twenty-five (925) patients and their private physicians were asked to answer a questionnaire. More than half of the hemodialysis (HD) patients had an unknown etiology of their kidney disease. Diabetes, polycystic kidney disease (PKD), chronic pyelonephritis and nephrosclerosis (NS) were the most commonly documented diagnoses. Consanguinity was present in 26% of the total HD population. More consanguineous patients with unknown renal etiology were diagnosed with their kidney diseases and initiated on dialysis before the age of 30 when compared with their non-consanguineous counter-parts (45% versus 33%, P<0.02 and 42% versus 27%, P<0.01), respectively. Similarly, consanguineous polycystic patients were diagnosed and started earlier on dialysis when compared with the non-consanguineous population (34% versus 12%, P<0.05 and 28% versus 8%, P<0.05), respectively suggesting a different disease pattern. Furthermore, the risk for family history of kidney disease was noticeable in the non-consanguineous population and significantly higher among the consanguineous patients (12% versus 18%, P<0.04). Consanguinity-associated kidney diseases affected all religious communities, in particular the Muslim and the Druze (36 and 39%), respectively versus 17% of the Christian community. Certain geographical areas were more involved than others such as the North, South and the Bekaa with the highest percentage (40%) in the latter. Socio-economical level was not a contributing factor. We conclude that the documentation of the underlying etiology in end-stage renal diseases (ESRD) seems to be deficient. Furthermore, consanguinity is prevalent in the Lebanese dialysis patients population, in particular the Muslim and the Druze communities. Consanguinity-associated kidney diseases pattern seems to differ from that of the general HD population by disease diagnosis and initiation at a younger age and a significantly higher risk for familial renal disease. It is a cultural phenomenon prevalent predominantly in the rural areas. We recommend a multi-approach including educational, informative and probably legislative strategy in order to limit and hopefully discourage consanguineous marriages.     

THE HLA-DRB1*0405 HAPLOTYPE IS MOST STRONGLY ASSOCIATED WITH IDDM IN ALGERIANS

Insulin-dependent diabetes mellitus (IDDM) in Caucasians is strongly associated with HLA-DR3-DQ2 and DR4-DQ8. In order to investigate the HLA class II associations with IDDM in Algerians, we have used polymerase chain reaction (PCR) and sequence specific oligonucleotide analysis (SSO) to identify DQA1, DQB1, and DRB1 alleles, haplotypes and genotypes in 50 unrelated IDDM patients and 46 controls from a homogeneous population in Western Algeria. Both DRB1*0301-DQA1*0501-DQB1*0201 (DR3-DQ2) and DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) haplotypes were found at increased frequencies among the patients compared to controls (45% vs. 13%, RR = 5.5, P_c < 10^-5 and 37% vs. 4%, RR = 12.9, P_c < 10^-4, respectively). Among the latter, in contrast to other Caucasian populations, only DRB1*0405-DQA1*0301-DQB1*0302 was significantly increased in the Algerian patients (25% vs. 1% in controls, RR = 30.3, P_c < 10^-3). Accordingly, the highest risk of disease was observed in DRB1*0301-DQA1*0501-DQB1*0201/DRB¹*0405-DQA1*0301-DQB1*0302 heterozygotes (34% in patients vs. 0% in controls; RR = 49; P_c < 10^-3). This observation and its comparison with DR-DQ haplotypes in other ethnic groups suggest that the DRB1*0405 allele which encodes an Asp57-negative β chain may contribute to IDDM susceptibility in a similar way as Asp57-negative DQβ chains.     

Monoclonal small (well-differentiated) lymphocytic proliferations of the gastrointestinal tract resembling lymphoid hyperplasia: A neoplasm of uncertain malignant potential

Three histologically benign-appearing or diagnostically equivocal small lymphocytic proliferations of the gastrointestinal tract were examined by fresh-frozen section immunohistologic techniques. In one case, a dense infiltrate in the small intestine, consisting of small lymphocytes with round nuclei, was limited almost entirely to the mucosa. In another case, a localized colonic polyp was formed by mucosal and submucosal lobules of benign-appearing lymphoid aggregates with centrally located germinal centers. The third case, a penetrating gastric ulcer, was surrounded by histologically hyperplastic lymphoid tissue which included germinal centers. The small lymphocytes in all three cases were strongly positive for B-cell-associated antigens (B1, B2, BA-1), and all exhibited monoclonal light-chain restriction. Even though treatment consisted only of surgical resection of the lesions, no patient has had progressive disease during follow-up periods ranging from 24 to more than 50 months. We believe that the infiltrates in these cases are analogous to the morphologically benign monoclonal small lymphocytic proliferations common to the lung and orbit and that they have an uncertain, but probably low, malignant potential.     

The control of chloride conductance in rat parotid isolated acinar cells investigated by photorelease of caged compounds

The control of Cl^– conductance in rat parotid isolated acinar cells was studied by combined use of whole-cell recording and flash photolysis techniques. Cells were voltage-clamped either at a membrane potential of –40 mV or stepped between –85 mV and 0 mV. Bath-applied carbachol and noradrenaline evoked Cl^– current at –85 mV and K⁺ current at 0 mV. Similar current activations resulted from the photolytic release of either inositol trisphosphate (InsP ₃) or Ca²⁺ by a brief near-UV flash. The peak amplitudes of the Cl^– conductance (at –85 mV), measured relative to the K⁺ conductance (at 0 mV), evoked by application of carbachol, noradrenaline or direct manipulation of cytosolic free calcium ([Ca²⁺]_i), were very similar, being 0.56±0.09 (mean±SEM,n=9), 0.52 ± 0.01 (n=7) and 0.46±0.06 (n=7). In contrast, the relative amplitude of the Cl^– conductance evoked by InsP₃ was much larger: 1.49±0.24 (n=9). Neither bath application of isoprenaline nor photolysis of caged cAMP induced any detectable membrane current. The most probable interpretation of these results is that the observed activation of Cl^– conductance by agonists can be explained by the elevation of [Ca²⁺]_i alone. In addition, the present results provide further support for the previously reported suggestion that the Cl^– channels and the Ca²⁺-release sites are co-localised [10].     

Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle

Citrin is a mitochondrial aspartate glutamate carrier primarily expressed in the liver, heart, and kidney. We found that adult-onset type II citrullinemia is caused by mutations in the SLC25A13 gene that encodes for citrin. In this report, we describe the frequency of SLC25A13 mutations, the roles of citrin as a member of the urea cycle and as a member of the malate-aspartate shuttle, the relationship between its functions and symptoms of citrin deficiency, and therapeutic issues.     

Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1

Longitudinal studies in Sudan show ethnic differences in incidence and clinical phenotypes associated with Leishmania donovani. Immunologically, bias in type 1 vs type 2 cytokine responses is important. To determine whether polymorphisms at IL4/IL9 or IFNGR1 contribute to susceptibility, we examined 59 multicase families of visceral leishmaniasis (VL) with/without post Kala-azar dermal leishmaniasis (PKDL). Multipoint nonparametric analysis (Allegro) linked IL4/IL9 to VL per se (P=0.002). Transmission disequilibrium testing with robust variance estimates confirmed association in the presence of linkage between VL per se and IL4 (P=0.008) but not IL9. Stepwise logistic regression analysis showed both IL4RP2 and IL4RP1 markers contributed significantly to the association, suggesting a common disease-associated haplotype. In contrast, IFNGR1 was linked (P=0.031) and associated (P=0.007) to PKDL but not VL or VL per se. Hence, polymorphism in a type 2 cytokine gene influences underlying susceptibility to VL, whereas IFNGR1 is specifically related to susceptibility to PKDL.     

Susceptibility pattern and molecular type of species-specific Candida in oropharyngeal lesions of Indian human immunodeficiency virus-positive patients

A study of oropharyngeal candidiasis (OPC) in Indian human immunodeficiency virus (HIV)/AIDS patients was conducted over a period of 15 months. This study revealed that 75% of the HIV/AIDS patients had OPC. MIC testing revealed that 5% of the Candida isolates were fluconazole resistant. A correlation between CD4(+)-T-cell counts and development of OPC in HIV/AIDS patients was also observed. Molecular typing of C. albicans isolates showed that all were genetically unrelated.