Aberrant secretors in donors and patients with duodenal ulcer

Results of the screening of aberrant (paradoxal) secretors in 14372 healthy donors and 614 patients with ulcus duodeni are presented. An extremely high frequency of aberrant secretors was established (12.6%) in patients with ulcus duodeni in comparison to donors (0.10%). A new type of aberrant secretors was registered in patients of A1 and A1B blood groups. Their salivas normally inhibited anti-A sera, but the expected inhibition of anti-A1 reagents (dolichos biflorus) could not be observed. The data of comparative quantitative investigations of the inhibiting strength of the ABH antigen in salivas of normal secretors, nonsecretors and aberrant secretors are presented. Various theoretical explanations of aberrant secretors are discussed.     

Multicenter study on the immunogenicity and safety of two recombinant vaccines against hepatitis B

The immunogenicity and safety of a new recombinant hepatitis B vaccine from the Instituto Butantan (Butang) were evaluated in a multicenter, double-blind, prospective equivalence study in three centers in Brazil. Engerix B was the standard vaccine. A total of 3937 subjects were recruited and 2754 (70%) met all protocol criteria at the end of the study. All the subjects were considered healthy and denied having received hepatitis B vaccine before the study. Study subjects who adhered to the protocol were newborn infants (566), children 1 to 10 years old (484), adolescents from 11 to 19 years (740), adults from 20 to 30 years (568), and adults from 31 to 40 years (396). Vaccine was administered in three doses on the schedule 0, 1, and 6 months (newborn infants, adolescents, and adults) or 0, 1, and 7 months (children). Vaccine dose was intramuscular 10 microg (infants, children, and adolescents) or 20 microg (adults). Percent seroprotection (assumed when anti-HBs titers were > 10 mIU/ml) and geometric mean titer (mIU/ml) were: newborn infants, 93.7% and 351.1 (Butang) and 97.5% and 1530.6 (Engerix B); children, 100% and 3600.0 (Butang) and 97.7% and 2753.1 (Engerix B); adolescents, 95.1% and 746.3 (Butang) and 96% and 1284.3 (Engerix B); adults 20-30 years old, 91.8% and 453.5 (Butang) and 95.5% and 1369.0 (Engerix B); and adults 31-40 years old, 79.8% and 122.7 (Butang) and 92.4% and 686.2 (Engerix B). There were no severe adverse events following either vaccine. The study concluded that Butang was equivalent to Engerix B in children, and less immunogenic but acceptable for use in newborn infants, adolescents, and young adults.     

Adjuvant can improve protection induced by OMV vaccine against Neisseria meningitidis serogroups B/C in neonatal mice

Meningococcal outer membrane vesicle (OMV) vaccines are weak antigens in infants. This study aimed at investigating alternative adjuvants for induction of functional antibodies in newborn mice. Serogroup B/C anti-meningococcal vaccines, consisting of capsular polysaccharide from serogroup C (PSC) conjugated to OMV from one serogroup B serosubtype prevalent in Brazil, combined with OMV from another prevalent serosubtype, were tested in newborn and adult mice with the following adjuvants: aluminum hydroxide, MPL (monophosphoryl lipid A), Titermax and MF59. Total IgG, IgG avidity index determination and bactericidal assay were performed with sera from immunized mice. Antibodies induced against PSC in newborn mice showed avidity and bactericidal titers, similar to those obtained in adult mice, independently of the adjuvant. Evidence is presented that the inclusion of MF59 enhanced the immune response against OMV in newborn mice.     

Production and excretion of nitrate by human newborn infants: neonates are not little adults.

Endothelium-derived relaxing factor, identified as nitric oxide or its adducts, is metabolized to nitrate and excreted in the urine. Since blood pressures are lower in newborn infants compared to adults, we hypothesized that newborn infants would have increased excretion of nitrate on the day of birth. Neonatal urine was collected before 24 h of age when exogenous intake of nitrate was low. Two different analytical methods showed that nitrate accounted for >99% of nitrogen oxides in urine of healthy neonates and adults. The absolute micromolar concentration of nitrate in urine from infants was significantly below that of adults. When nitrate content was standardized for the reduced renal function in the newborn infant (creatinine content) and body mass (kilogram weight), the concentration of nitrate in neonatal urine was significantly higher than that of adults. Nitrate concentrations in the urine of prematurely born infants were twice that of nitrate measured in urine from term infants. These findings suggested that nitric oxide is produced in larger intravascular quantities in newborn infants versus adults. Thus, we postulated that nitric oxide released from a nitrosothiol would be metabolized to nitrate more readily by neonatal erythrocytes compared to red blood cells obtained from adults. Neonatal erythrocytes, suspended at concentrations of 8, 12, or 16 g per deciliter of hemoglobin, produced 1.7- to 2.1-fold more nitrate than equivalent hemoglobin concentrations of adult erythrocytes that were each incubated with S-nitroso-N-acetylpenicillamine (100 microM) over a 2-h period. Taken together, the studies of urinary nitrate in newborn infants and the ability of neonatal erythrocytes to generate nitrate are consistent with a robust production of nitric oxide immediately after birth.     

Salivary gland antigens of Ixodes dammini are glycoproteins that have interspecies cross-reactivity.

Serum from rabbits and rats exposed to Ixodes dammini adults and larvae, respectively, contain antibodies to a large number of antigens in salivary gland homogenates from adult ticks that cross react with the antigens of a closely related species, Ixodes scapularis, and significantly with Dermacentor variabilis antigens. The salivary gland antigens of I. dammini are glycoproteins composed of both N- and O-linked carbohydrate chains. The antigenic determinants reside in both the polypeptide and carbohydrate chains.     

Nitrate reductase activity of bacteria in saliva of term and preterm infants

The salivary glands of adults concentrate nitrate from plasma into saliva where it is converted to nitrite by bacterial nitrate reductases. Nitrite can play a beneficial role in adult gastrointestinal and cardiovascular physiology. When nitrite is swallowed, some of it is converted to nitric oxide (NO) in the stomach and may then exert protective effects in the gastrointestinal tract and throughout the body. It has yet to be determined either when newborn infants acquire oral nitrate reducing bacteria or what the effects of antimicrobial therapy or premature birth may be on the bacterial processing of nitrate to nitrite. We measured nitrate and nitrite levels in the saliva of adults and both preterm and term human infants in the early weeks of life. We also measured oral bacterial reductase activity in the saliva of both infants and adults, and characterized the species of nitrate reducing bacteria present. Oral bacterial conversion of nitrate to nitrite in infants was either undetectable or markedly lower than the conversion rates of adults. No measurable reductase activity was found in infants within the first two weeks of life, despite the presence of oral nitrate reducing bacteria such as Actinomyces odontolyticus, Veillonella atypica, and Rothia mucilaginosa. We conclude that relatively little nitrite reaches the infant gastrointestinal tract due to the lack of oral bacterial nitrate reductase activity. Given the importance of the nitrate-nitrite-NO axis in adults, the lack of oral nitrate-reducing bacteria in infants may be relevant to the vulnerability of newborns to hypoxic stress and gastrointestinal tract pathologies.     

The AB blood group system of cats

Holmes (1950) and Eyquem. Podliachouk & Milot (1962) classified feline erythrocytes into two types according to their reactions with naturally occurring antibodies in cats' plasmas. Eyquem et al. (1962) designated the two antigens, A and B. and this nomenclature has been retained in the present study. The blood group system. AB. was investigated in more detail, both genetically and serologically. Frequencies of 73.3 % A and 26.3 % B were found in a survey of 1895 Brisbane cats and in addition, a new phenotype. AB. was discovered with a low incidence of 0.4 %.The results of the serological testing and limited family information suggested that the AB phenotype is inherited and not due to blood chimaerism. Preliminary genetic studies indicated that the A gene is dominant to the B in the usual situation and hypotheses to explain the occurrence of the AB phenotype are discussed.
The incidence of naturally occurring antibodies was investigated in cats, with 1895 of blood type B having anti-A and only 35 % of type A having anti-B. No subgroups of the A and B antigens were detected and no blood group substances were found in the salivas of 37 cats. There was no evidence of any serological relationship of the feline A and B antigens with the human ABO antigens.     

Quantitation of antibody uptake on A group erythrocytes using immunoautoradiography and monoclonal IgM anti-A

The number of antibody molecules on individual erythrocytes was counted in A1, A2, A3 B and A group individuals using immunoautoradiography (IAR) and monoclonal IgM anti-A1. Quantitation was also done for A group pregnant women. The number of antibody molecules on different red cells of an individual varied widely. Gross variations were also noted in cells of different individuals from one and the same group. The mean values of the uptake of the number of antibody molecules showed the following range A1 greater than A2 greater than Ax greater than A3B. When compared to the average for total A1 adults, red cells of pregnant women and newborn infants showed a 10.7% and 19.7% reduction respectively, in antibody uptake. The mean number of antibody molecules per A1 adult red cells was 5.6 +/- 3 X 10(4), while A2 had 0.85 +/- 0.35 X 10(4) molecules, thus showing a significant quantitative variation.     

Leucocyte energy metabolism. V. Glycolytic and hexose monophosphate shunt enzymes in leucocytes from adults and newborn infants.

The activities of ATP-consuming and ATP-producing steps of the Embden-Meyerhof pathway, as well as other glycolytic enzymes (phosphoglucomutase and enolase) and glucose-6-phosphate dehydrogenase are lower in leucocytes from cord blood than in white cells from adults. These results are related to previous observations (reduced anaerobic glycolysis and nitroblue tetrazolium-test in leucocytes from newborn infants) and discussed in connection with the fact that newborn infants are more susceptible to infections than normal adults.     

Differential expression of isoproterenol-induced salivary polypeptides in two mouse strains that are congenic for the H-2 histocompatibility gene complex

Two inbred mouse strains, A/Snell and A.Swiss, which were produced as congenic with regard to the H-2 histocompatibility gene complex, are homozygous for two different groups of isoproterenol-induced salivary polypeptides (IISP). These polypeptides, which have been considered as markers of the hypertrophic growth of the parotid acinar cells, are members of the complex family of salivary proline-rich proteins (PRP) on the basis of both their massive accumulation in the parotid acinar cells in response to chronic isoproterenol, secretory character, high solubility in trichloroacetic acid and metachromatic staining by Coomassie blue. IISP expressed in both mouse strains were identified by unidimensional SDS-polyacrylamide electrophoresis and Coomassie blue staining both in parotid gland homogenates and in whole salivas obtained from mice repeatedly stimulated at 24-h intervals with isoproterenol. Parotid glands from 40 mice (20 A/Snell and 20 A.Swiss) and salivas from 270 mice (200 A/Snell and 70 A.Swiss) were analyzed. One of the congenic strains (A/Snell) expressed five IISP (Mr 65, 61, 51.5, 38, and 37 kDa) and the other strain (A.Swiss) expressed six IISP (Mr 59, 57, 54.5, 46, 36, and 34 kDa). No inter-individual intra-strain variations were observed, thus defining strain-associated patterns of IISP (PRP).     

Antigens of the Ii System on Lymphocytes

USUALLY Ii specificity is assigned to cold agglutinins on the basis of their reactions with the red cells of human adults (adult red cells) and newborn infants (cord red cells). Those which react more strongly with adult red cells are said to detect I antigen and are designated anti-I; those which react more strongly with cord red cells are said to detect i antigen and are designated anti-i^1,2. We have now found that I and i antigens can be easily detected on lymphocytes.     

Population and molecular-genetic aspects of Haemophilia A and Haemophilia B in Uzbekistan

The present study summarizes results of retrospective epidemiological and molecular-genetic investigations of Haemophilia A and Haemophilia B in Uzbekistan. In the period from 1991 to 2004, a combined total of 1304 cases of Haemophilia A and Haemophilia B were recorded in the republic. The morbidity index varied from 0.75 to 1.46 per 10000 newborn male infants. The mean birth rate of patients with Haemophilia A and Haemophilia B amounted to 1: 8735 (1.14 × 10^?4) of newborn male infants. Features of certain DNA-polymorphisms in the genes of blood coagulation factors VIII and IX in the Uzbek population were analyzed. The frequencies of alleles were studied and the information value of these genetic markers for ascertaining genetic carriage and prenatal diagnosis of Haemophilia A and Haemophilia B was determined. Results of DNA diagnosis of Haemophilia A and Haemophilia B are summarized.     

Sequence of action of genes at the secretor, H, ABO and Lewis loci.

It is argued that Lewis genes are responsible for adding specificity to glycoprotein molecules after the activities of the secretor, H and ABO genes, respectively, have been expressed. This conclusion is based on the results of studies on the expression of ABO and Lewis antigens in salivas from Australian aborigines, and on biochemical results. A simple figure illustrating the antigens determined on red cells and in body secretions as a result of the action of these genes, in their correct order--secretor, H, ABO, Lewis--is presented.     

PRB2/1 fusion gene: a product of unequal and homologous crossing-over between proline-rich protein (PRP) genes PRB1 and PRB2.

The PRB2/1 fusion gene is produced by homologous and unequal crossing-over between PRB1 and PRB2 genes that code for basic salivary proline-rich proteins (PRPs). To determine the molecular basis for the PRB2/1 fusion gene, the DNA sequence was determined for the PRB2/1 gene and was compared with those of the PRB1 and PRB2 genes. From these comparisons, the crossing-over is postulated to occur in a 743-bp region of identity, with only 1-bp mismatch between the PRB1 and PRB2 genes, in the third intron outside the coding region of the two genes. This region of virtual complete identity is the largest found between any of the six closely linked PRB genes and may facilitate recombination. Since the coding region of PRB1 is completely absent from the PRB2/1 gene, salivas from two white PRB2/1 homozygotes were studied to determine which polymorphic PRPs were missing from the salivas. Polymorphic PRPs Pe, PmF, PmS, and Ps were found to be missing from the salivas. However, a white individual lacking the same salivary PRPs is a PRB2/1 heterozygote with one PRB1 allele. The explanation for the missing salivary proteins in this individual is unknown. The PRB2/1 gene is relatively frequent in several populations of unrelated individuals, including American blacks (n = 41), American Utah whites (n = 76), and mainland Chinese (n = 131), with gene frequencies of .22, .06, and .09, respectively. Evidence for the occurrence of PRB1/2 heterozygotes is also presented.     

Genetic polymorphisms of Pe and Po salivary proteins with probable linkage of their genes to the salivary protein gene complex (SPC)

Two new genetic polymorphisms (Pe and Po) are found in human parotid saliva. Each polymorphism is determined by the autosomal inheritance of one expressed (dominant) and one unexpressed (recessive) allele. Autosomal inheritance is supported by studies of 63 families including 264 children for Pe and 57 families including 242 children for Po. For randomly collected salivas, gene frequencies in 317 whites are Pe+ = 0.76 and Pe- = 0.24; in 408 whites, Po+ = 0.75 and Po- = 0.25; in 51 blacks, Pe+ = 0.76 and Pe- = 0.24; and in 59 blacks, Po+ = 0.77 and Po- = 0.23. Both Pe and Po proteins react immunologically with polyclonal antisera prepared to proline-rich proteins PRPs. The Pe protein has an isoelectric point of approximately pH 6.1-6.3, and the Po protein has an isoelectric point greater than pH 8.0. In randomly collected salivas, the Pe and Po proteins are associated with other known salivary PRPs. The Pe protein is most strongly associated with the CON 1 and Ps proteins, is less strongly associated with the Pr and Pa proteins, and is not significantly associated with the PmF, PmS, PIF, Db, Con 2, or Gl proteins. If it is assumed that the strength of these associations (presumed linkage disequilibrium) may be related in part to map distance, then these data roughly fit the linear order of PRP genes as previously determined from recombination data derived from family linkage studies. The Po protein is associated with the PmS protein. There is evidence for probable linkage of Pe and Po to the SPC (salivary protein gene complex): Pe to Pa (nine families, lod score at theta = 0 is 2.67) and Po to CON 2 (three families, lod score at theta = 0 is 2.35).     

Protein secretion from the cat parotid gland on nerve stimulation

1. The output and composition of proteins in nerve stimulated saliva samples were compared. 2. Protein output upon parasympathetic stimulation was higher than following sympathetic stimulation and was accompanied by an obvious degranulation of acini with the former but not the latter. These events are the converse of those in the rat parotid gland. 3. Superimposition of sympathetic upon parasympathetic stimulation caused an augmented output of salivary protein. 4. Electrophoresis of salivas revealed differences between individual cats in protein composition but not between differently stimulated salivas.     

Genetic polymorphism of vitamin B12 binding (R) proteins of human saliva detected by isoelectric focusing

Genetic polymorphism of the vitamin B12 binding (R) proteins of parotid saliva is determined by autosomal inheritance of codominant alleles. This hypothesis is supported by studies in 43 families including 152 children. For randomly collected salivas from 143 whites, 104 blacks, and 75 Chinese, gene frequencies are as follows: for whites, Rs1=0.88, Rs2=0.12; for blacks, Rs1=0.94, Rs2=0.06; for Chinese, Rs1=1.00. This genetic marker is also shared by R proteins of milk, tears, and leukocytes. In the Rs 1--2 salivary type there is less labeling of the protein products of Rs2 v. Rs1 with 57Co B12 as assessed by the intensity of the bands on the autoradiogram. There is no evidence for close linkage (theta less than 0.01) between Rs and TC II (transcobalamin II) or between Rs and salivary protein locus Pr, Db, Gl, or Ps.     

Streptococcus group B in meningitis and infection of newborn infants

Streptococci were isolated from the liquor or blood of 102 newborn infants and 16 infants in the first month of their life, suspected of having purulent meningitis, in 22 cases (18,5%). 5 isolated streptococcal strains were classified with group B on the basis of their cultural, biochemical and serological features. All of these strains were isolated from newborn infants during the first 3-4 days of their life. The occurrence of group B streptococci among all examined newborn infants was 4.8%; among the newborns with the positive results of bacteriological examination (73 infants) this figure was as high as 6.8%. The authors emphasize the necessity of producing, on an industrial scale, diagnostic preparations for the identification of group B streptococci playing a significant role in septic diseases and meningitides in newborns.     

ABO Blood Group Is Associated with Response to Inhaled Nitric Oxide in Neonates with Respiratory Failure

Background

Inhaled nitric oxide (iNO) reduces death or need for extracorporeal membrane oxygenation (ECMO) in infants with persistent pulmonary hypertension of the newborn (PPHN). However, the response to iNO is variable and only 50–60% of infants demonstrate a response to iNO. It is not known why only some infants respond to iNO. Adults and children with blood groups B or AB do not respond as well to iNO as those with blood groups O/A.

Methods/Principal Findings

To determine if blood group was associated with iNO response in newborn infants, a retrospective medical record review was done of infants admitted to a regional NICU from 2002-9 with a diagnosis of PPHN. Data were collected during the first twelve hours post-initiation of treatment. Of 86 infants diagnosed with PPHN, 23 infants had blood group A [18 received iNO], 21 had group B [18 with iNO], 40 had group O [36 with iNO], and 2 had group AB [both received iNO]. Change in PaO₂/FiO₂ was less in infants with blood group A, of whom less than half were responders (ΔPaO₂/FiO₂>20%) at 12 h versus 90% of infants with either O or B. Race, sex, birth weight, gestational age, Apgar scores at 1 and 5 minutes, and baseline PaO₂/FiO₂ were similar among groups. Outcomes including need for ECMO, death, length of ventilatory support, length of iNO use, and hospital stay were statistically not different by blood groups.

Conclusions/Significance

Our results indicate that blood group influences iNO response in neonates. We hypothesize that either there is genetic linkage of the ABO gene locus with vasoregulatory genes, or that blood group antigens directly affect vascular reactivity.     

Antibodies to Streptococcus pneumoniae antigens in newborn infants

The levels of antibodies to capsular polysaccharide antigens of pneumococci (serotypes 1, 3, 6B, 8, 9N, 15F, 23F), C-polysaccharide and protein antigen of pneumococci in the blood sera of 38 newborn infants at the moment of their birth (umbilical blood) and on the 5th or 6th day of their life, in their mothers' blood sera, as well as in the colostrum and milk of 48 nursing women, have been studied by means of the enzyme immunoassay. The study showed that in the normal course of pregnancy antibodies to pneumococci were transferred transplacentally from the mother to the fetus. Though in most cases their content in the blood of newborn infants was lower than that in maternal blood, it exceeded the average level of antipneumococcal antibodies in children aged 3-12 months. In the milk of nursing mothers considerable amount of IgA antibodies to pneumococci was detected, which might be an additional protective factor with respect to pneumococcal infection in infants.