Blocking B7-1/CD28 Pathway Diminished Long-Range Brain Damage by Regulating the Immune and Inflammatory Responses in a Mouse Model of Intracerebral Hemorrhage

Acute brain injuries can activate bidirectional crosstalk between the injured brain and the immune system. The immune system, particularly T lymphocytes and cytokines, has been implicated in the progression of brain injury after intracerebral hemorrhage (ICH). Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) binding cognate receptor provides a secondary signaling to T cell activation. The aim of our study was to explore the effects of anti-B7-1 antibody on the development and prognosis of cerebral hemorrhage and to investigate the possible underlying mechanism. Mice were inner canthus veniplex administered with anti-B7-1 antibody at 10 min and 24 h after ICH and sacrificed on the third day after ICH. Immune function was assessed via splenocyte proliferation assay and organism index, respectively. IFN-γ and IL-4 were detected by enzyme-linked immuno sorbent assay. The cerebral edema was evaluated via brain water content. The levels of autophagy and apoptosis related proteins were measured by western blotting analysis. In addition, functional outcome was studied with pole-climbing test and morris water maze. The mice were weighed on 0, 1, 3, 14 and 21 days after ICH. The treatment with anti-B7-1 antibody significantly lowered immune function, and reduced the latency of water maze on 18 and 20 days, the ratio of IFN-γ/IL-4 as well as body weight on day 3 after cerebral hemorrhage. Our study suggests that in the cerebral hemorrhage mice brain anti-B7-1 antibody may reduce long-range brain damage by reversing immune imbalance.     

A significant age shift of the human parvovirus B19 antibody prevalence among young adults in Japan observed in a decade.

A seroepidemiological study on human parvovirus (B19) in Japan was undertaken with serum samples randomly collected from healthy Japanese populations (416 in 1973, 675 in 1984 and 508 in 1987/88). All samples were tested for anti-B19 IgG antibody by the indirect antigen-capture ELISA. The antibody prevalence for ages 0-9 years old in 1984 was significantly higher (16%) than that in 1973 (2%), whereas those for ages 20-29 years and 30-39 years were significantly lower in 1984 (20% and 56%) than in 1973 (67% and 80%) (p < 0.005). After the erythema infectiosum (EI) outbreak in 1986/87, the antibody prevalences for ages 5-9, 10-14 and 15-19 years were 40-85% in Fukuoka, 0-10% in Gunma, and 21-41% in Chiba reflecting each EI incidence in these three prefectures, whereas those for ages 20-29 years remained low (< 20%). These data indicate that B19 virus was transmitted mainly among children and no significant incidence of B19 virus infection in adults has occurred since 1973, resulting in a notable shifting of B19 susceptibility toward older ages including child-bearing females.     

Incidence of Rubella Antibodies in Female Subjects

Sera from females aged 1 to 40 years were assayed for rubella virus antibodies. Results showed that by age 14 years, 60% had antibodies and that by 19 years, 70% were positive. This figure rose to 80% by 24 years of age and remained unchanged in older age groups.A comparison of the incidence of high and low levels of antibodies in each age group revealed that antibody levels fell between ages 20 and 40 years. Only 20% of individuals in the latter group had a high antibody level compared to 80% in the former.These results are discussed as they relate to the problems of reinfection and possible vaccination procedures.     

The B cell surface molecule B1 is functionally linked with B cell activation and differentiation

The B1 molecule is a 32,000 m.w. phosphorylated cell surface protein expressed exclusively by B cells from the mid pre-B until the plasma cell stage of differentiation. Two monoclonal antibodies (gamma 2a and mu) reactive with this molecule were used to assess the role of B1 in B cell activation, proliferation, and differentiation. The anti-B1 antibodies at concentrations ranging from 0.1 to 100 micrograms/ml significantly inhibited B cell proliferation induced by anti-mu antibodies, Staphylococcus aureus Cowan strain 1, activated T cells, and Epstein Barr virus. Although capable of inhibiting proliferation, anti-B1 antibody in soluble form or coupled to beads did not activate B cells or induce proliferation. Antibodies of comparable isotypes or against other B cell-restricted antigens, including B2, B4, B5, and HB-5, did not inhibit activation. Pretreatment of B cells with anti-B1 antibody did not inhibit activation, indicating that B cells had to be cultured with anti-B1 antibody for anti-B1-mediated inhibition to occur. Maximum inhibition was obtained when anti-B1 antibody was added at the initiation of culture. In agreement with this, growth factor-dependent proliferation of preactivated B cells was not inhibited by anti-B1 antibodies. Comparable inhibition of B cell activation was noted with antibodies reactive with class II antigens of the major histocompatibility complex with the exception that anti-B1 antibody inhibited immunoglobulin secretion in pokeweed mitogen assays, whereas anti-DR antibody did not. These results suggest that the B1 molecule may serve a central role in the regulation of B cell activation and differentiation.     

陕西省育龄期妇女风疹抗体水平调查

2006年在陕西省铜川、延安、宝鸡、渭南四市随机抽取20~40岁育龄期妇女共172人进行风疹IgG(RV-IgG)抗体水平调查,总阳性率87.2%,其中20~24岁组阳性率最高(95.6%),随着年龄的增长,阳性率和抗体几何平均浓度(GMC)有下降的趋势;不同居住地育龄妇女风疹抗体水平无显著性差异。这次调查反映了陕西省育龄期妇女风疹抗体水平的基本状况,为今后制定有效的免疫预防策略提供了依据。     

Value of repeated blood pressure measurements in children--the Brompton study.

Systolic blood pressure were measured in 1797 infants aged 4 days and then repeated at 6 weeks, 6 months, 1 year and then yearly until 4 years of age. The mean pressure rose from 76 mm Hg at 4 days to 96 mm Hg at 6 weeks but did not vary appreciably between subsequent measurements. Serial correlation coefficients of blood pressure adjusted for weight and degree of consciousness were calculated, comparing measurements at each age. At ages under 1 year the correlation coefficients were relatively weak, though most were significant (r < 0.2). As the children grew older these serial correlations became stronger, so that the correlation coefficient in blood pressure between ages 3 and 4 years was 0.47. These observations suggest that "tracking" for blood pressure starts at about 1 year and is much stronger by 4 years. Taken in conjunction with the findings of other long-term follow-up studies in older children, this suggests that children develop blood pressures indicative of their adult values between 1 and 4 years.     

The Ontogeny of Apomorphine-Induced Alterations of Neostriatal Dopamine Release: Effects on Spontaneous Release

The effects of apomorphine (0.05, 0.1, and 1.0 mg/kg, s.c.) on the extracellular levels of dopamine and the dopamine metabolite 3, 4-dihydroxyphenylacetic acid were studied through the use of in vivo microdialysis in the neostriatum of developing and adult rats. Fifteen-minute samples were collected from urethane-anesthetized rats 5, 10–11, 21–22, and 35–36 days old and adults and quantified by HPLC with electrochemical detection. Apomorphine attenuated extracellular levels of dopamine in all age groups, suggesting that the dopamine autoreceptor modulating release in the neostriatum is functional by 5 days of age. A dose-response effect of apomorphine on extracellular dopamine was observed in all age groups except at 10–11 days of age. Extracellular levels of 3, 4-dihydroxyphenylacetic acid were also significantly decreased in all age groups, consistent with the hypothesis that synthesis-modulating dopamine autoreceptors in the neostriatum are functional by 5 days of age. Apomorphine had a significantly greater effect on extracellular 3, 4-dihydrpxyphenylacetic acid levels at the 0.05 and 0.1 mg/kg doses in the 5- and 10–11-day-old age groups compared with the other ages. Absolute levels of extracellular dopamine were significantly attenuated at 5 days of age compared with the other ages, and absolute levels of extracellular 3, 4-dihydroxyphenylacetic acid monotonically increased with age.     

Seroepidemiologic study of arbovirus infections in the north-east and south of Thailand

Blood specimens were collected from villagers in Khon-Kaen province, in the north-eastern region, and in Songkhla province, in the southern region of Thailand in the pre- and post-epidemic seasons of hemorrhagic fever. The hemagglutination inhibition antibody titers of the specimens were measured against dengue virus type 2, type 4, Japanese encephalitis virus and chikungunya virus. In general, Khon-Kaen villagers showed higher levels of HI antibodies against these arboviruses than Songkhla villagers and in both areas the antibody level against chikungunya virus, a group A arbovirus, was usually much lower than those against group B arboviruses. Specimens from Khon-Kaen province had such high antibody positive rates for group B arboviruses (80-100%) from an early age (3-4 years), in the pre-epidemic season, that scarcely any increase in the positive rate was observed in the post-epidemic season. The positive rate in specimens from Songkhla province was not so high in the pre-epidemic season and some increase was seen in the post-epidemic season, especially in lower age groups (3-4 to 7-9 years). The patterns of HI antibody titers in different age groups in the Khon-Kaen and Songkhla provinces were also compared. The patterns changed with increase of ages and were also different with different viruses. The patterns for chikungunya virus were quite different from those for dengue type 2, type 4 and Japanese encephalitis virus. These results suggest that people in Khon-Kaen are exposed to group B arbovirus infections more often in childhood and attain high antibody levels more rapidly than people in Songkhla.     

2003-2008年我国实验猴BV抗体检测结果及抗体水平变化规律的分析

目的对近年来我国实验猴BV（猴疱疹病毒Ⅰ型）抗体检测结果进行比较分析,以了解我国实验猴BV感染情况及其抗体水平变化规律,为我国实验猴质量控制及标准化提供依据。方法根据国标中ELISA方法 ,对2003～2008年我国11个单位送检的2个品种猴血清进行BV抗体检测,并对检测结果进行统计分析。结果检测的4612份猴血清中,有1843份BV抗体呈阳性,阳性率为39.96%;6年中检测猴群BV抗体阳性率基本在30%～50%。幼年（≤2岁）、青年（2.1～4.0岁）、成年（4.1～6.5岁）、老年（≥6.5岁）4个不同年龄段猴BV感染率分别为26.28%、31.53%、53.74%、87.27%。不同年龄感染率差异显著（P〈0.01）。雌猴BV感染率（35.91%）高于雄猴（34.93%）,但两者差异不显著（P〉0.05）。结论不同年龄猴BV感染率不同,随着年龄的增长BV感染率升高。     

Cold agglutinin with anti-B specificity in an A1B subject]

A high titre cold autoagglutinin with anti-B specificity was found in the serum of an A1B group individual. It was associated with a low titre anti-I. This anti-B agglutinated most cells having a B antigen (normal B, A1B, A2B, from adult and cord bloods, B3), but failed to agglutinate Bx Cis-AB and Bh cells. Nevertheless, all these cells absorbed the anti-B SER at low temperatures. Fixation elution tests were also positive on the patient's cells and three consecutive absorptions on these cells completely removed the anti-B activity. The Coombs test was positive with anti-complement anti-globulin when the cells were sensitized by the serum at 4 degrees C. It was negative when the cells were sensitized at 37 degrees C. The patient did not show any sign of haemolysis. The anti-B was a IgM Kappa. Its reaction with normal B cells had an enthalpy change of - 36-000 cal./mole, i.e. very different from O ANd A individuals, but similar to that of the erythrocytic I antigen - anti-i antibody reaction. Quantitative measurements showed the erythrocyte B antigen similar to that of control A1B cells.     

Direct Antiglobulin Reaction in ABO-Haemolytic Disease of the Newborn

The minimum number of IgG anti-A (or anti-B) molecules detectable on A or B red cells by the antiglobulin reaction was found to be the same—that is, about 150 molecules per red cell—with newborn as with adult cells. Furthermore, the ratio of anti-IgG bound to IgG anti-A (or anti-B) molecules was the same whether the anti-A (or anti-B) molecules were present on newborn or on adult cells and was similar to that found for anti-IgG bound to IgG anti-Rh.In 15 infants (11 group A, 4 group B) with haemolytic disease of the newborn due to ABO-incompatibility the amount of anti-A or anti-B on the red cells ranged from 0·25 to 3·5 μg antibody per ml red cells, corresponding to 90-1,320 antibody molecules per cell; only five infants had more than 0·55 μg antibody per ml of red cells. These amounts are far smaller than those found in most moderate or severe cases of Rh-haemolytic disease.It is concluded that the weak direct antiglobulin reactions observed in ABO-haemolytic disease are due simply to the fact that the number of anti-A (or anti-B) molecules on the infant''s red cells is at the lower limit of sensitivity of the test. Since ABO-haemolytic disease can be quite a severe process it seems probable that IgG anti-A and anti-B molecules are more effective than anti-Rh molecules in bringing about red cell destruction.     

Activity of pulmonary surfactant after blocking the associated proteins SP-A and SP-B

To investigate the role of the pulmonary surfactant-associated proteins SP-A and SP-B, the respective monoclonal antibody (anti-A or anti-B) was added to porcine pulmonary surfactant at a weight ratio of 1:2, and the mixtures were tested on surfactant-deficient immature newborn rabbits (gestational age 26 days). Under pentobarbital sodium anesthesia and mechanical ventilation with a 25-cmH2O peak insufflation pressure, the tidal volumes of the animals given surfactant alone and of those given surfactant containing anti-A were 27.9 +/- 5.1 and 25.1 +/- 9.6 (SD) ml/kg, respectively, whereas that of those given surfactant with anti-B was 5.8 +/- 3.6 ml/kg (P less than 0.05). The surface adsorption times of surfactant alone and of anti-A-containing surfactant were less than 0.8 s compared with greater than 120 s (P less than 0.01) for anti-B-containing surfactant. The anti-B suppressed the surfactant activity until the weight ratio was decreased to 2:100. The role of SP-A could not be clarified, but it was concluded that SP-B is an essential factor for surfactant activity.     

Synthesis of natural allohemagglutinins of the ABO system in healthy children aged 3 months to 3 years

The work was carried out to establish the titre and score of haemagglutination of natural anti-A and anti-B antibodies in healthy children during the first three years of life. The material studied included 900 healthy children aged between 3 months and 3 years and 100 adults serving as controls. The method of test tube haemagglutination was used for determining the titre and score of alloagglutinins in relation to standard erythrocytes always obtained from the same donors. In addition, in 72 children and 10 adults the levels of IgG, IgA and IgM were determined quantitatively. A statistical analysis of the results showed that the levels of anti-A and anti-B alloagglutinins were relatively high at the age of 3 months / about 25% of the adult levels / and increased very rapidly in the first years of life reaching about 90% of the adult level at the end of the 3rd year of life. Besides that, it was demonstrated that it is useful in clinical practice to use the titre and score of natural alloagglutinins as indicators of humoral immunity, especially in children in the first years of life. Acceleration was demonstrated in the intensity of haemagglutination of natural antibodies in the last 40 years since their titre in the contemporary infantile population / up to the age of 1 year / is about 50% higher than that found in 1929. These findings suggest that increased immune reactivity of children observed presently may be due to prophylactic vaccinations.     

Changes in Leydig cell function during sexual maturation in the mouse

Changes in androgen production by isolated Leydig cells were evaluated from 20 through 60 days of age in the mouse. Leydig cells were obtained by mechanical dissociation of testes, purified by centrifugation in metrizamide gradients, and incubated with increasing concentrations of human chorionic gonadotropin (hCG). Testosterone and 5 alpha-androstane-3 alpha, 17 beta-diol (androstanediol) were measured by radioimmunoassay in samples of cells plus medium. Sensitivity of mouse Leydig cells, evaluated as the concentration of hCG that elicited half-maximum androgen responses, was essentially the same at all ages. Maximum testosterone production increased by about 20-fold from 20 to 45 days of age but was no greater at 60 days than at 45 days. Maximum androstanediol production increased by about 3- to 4-fold from 20 to 25 days and declined after 30 days of age. Androstanediol predominated over testosterone by about 2-fold at 20 days; this relationship was reversed by 30 days, and at later ages testosterone greatly predominated over androstanediol (by at least 4- and 6-fold at 45 and 60 days of age, respectively). Maximum total androgen production, estimated from the sum of the values for testosterone and androstanediol, increased by about 7-fold from 20 to 30 days of age and remained essentially constant thereafter. These results are compared with those from previous studies of the rat.     

The effect of perinatal 60Co gamma radiation on brain weight in beagles

Beagle dogs were given single, whole-body 60Co gamma-radiation exposures at one of three prenatal (8, 28, or 55 days postcoitus) or three postnatal (2, 70, or 365 days postpartum) ages to evaluate the relative radiosensitivity of various stages of brain development. A total of 387 dogs received mean doses ranging from 0.16 to 3.83 Gy, and 120 dogs were sham-irradiated. Groups of dogs were sacrificed at preselected times from 70 days to 11 years of age. Brain weight decreased significantly with increasing dose in dogs irradiated at 28 or 55 days postcoitus or at 2 days postpartum. Irradiations at 28 days postcoitus were dramatically more effective in causing a reduction in brain weight than those at 55 days postcoitus or 2 days postpartum. Among dogs given 1.0 Gy or more and followed for up to 4 years, there was a radiation effect evident at all three sensitive exposure ages. Among dogs given lower doses and followed for up to 11 years, there was a significant decrease in brain weight in dogs given 0.80-0.88 Gy at 28 days postcoitus. All decreases in brain weight were present after normalization for radiation-induced reductions in skeletal (body) size. No specific morphologic changes were noted in the brains which showed the radiation-related reductions in size.     

Effects of cranial cervical ganglionectomy and castration of male lambs. II. 24 hour plasma profiles of luteinizing hormone, testosterone and prolactin

Male lambs were utilized in an experiment designed to evaluate the effects of cranial cervical ganglionectomy (GX), castration and age on hormone secretion profiles. Blood plasma samples were collected at hourly intervals for 24 hours from 24 lambs aged 101 days and 20 lambs aged 277 days, then assayed for concentrations of luteinizing hormone (LH), testosterone and prolactin. At both ages pulsatile secretion of LH and testosterone was confirmed, but no circadian rhythm of LH testosterone or prolactin secretion was detected. Castration elevated LH levels significantly at both ages. GX and its interaction with castration had no effect on LH secretion at 101 days, but at 277 days these factors were significant, largely due to elevated levels being recorded from GX castrates. GX did not affect testosterone levels in entire animals at either age, while plasma from castrates contained no detectable testosterone. GX reduced prolactin concentrations at 101 days of age (summer) but elevated them at 277 days of age (winter). Castration and the interaction of castration with GX had no significant influence on plasma prolactin levels at either age. This study confirmed that the pineal gland of sheep is involved in the regulation of prolactin secretion, and probably influences LH secretion as well.     

An auto-anti-b in an a1b person. Serological studies.

The serum of a patient (Mr. Lat) with the regular blood group A1 B contains an anti-B reacting with all cells having a B antigen except Bx and cis AB. The anti-B reacts at 4 degrees C and occasionally at room temperature as shown by agglutination, absorption-eluction and by thermo-dynamic assays. The antibody is regarded as an irregular autoantibody belonging to the group of the so called "suppressed" or "latent" antibodies.     

Plasma FSH and LH in prepubertal Booroola ewe lambs

Basal plasma concentrations (four 30-min samples) and GnRH-induced release of gonadotrophins were measured every 15 days between 30 and 90 days and at 110 days of age in Merino ewe lambs from the prolific Booroola ('B') flock (n = 18-23), the medium prolificacy ('T') flock (n = 14-20), and the 'O' flock (n = 4-8) of low prolificacy. At ages of 30 and 45 days B ewe lambs had mean basal plasma FSH concentrations of 145 and 122 ng/ml which were significantly higher (P less than 0.01) than those seen in T (45 and 53 ng/ml), and O (39 and 38 ng/ml) flock ewes. Between 60 and 110 days of age there were no significant differences between genotypes. The increment in FSH concentrations above basal levels induced by the subcutaneous injection of 100 micrograms synthetic GnRH was only significantly (P less than 0.05) greater in B than T and O genotype ewe lambs at 110 days of age but not at other ages. The basal plasma FSH differences between the B, T and O genotypes at 30 and 45 days of age were not consistently related to the size of litter in which lambs were born. At 30 days of age the mean plasma LH concentration of B, T, and O flock lambs were 2.6 +/- 0.5, 1.2 +/- 0.6 and 0.7 +/- 0.8 ng/ml respectively. These differences were not significant. At later ages there were also no significant differences between the genotypes with respect to basal LH, and the increase in LH induced by exogenous GnRH was always similar for the three genotypes.(ABSTRACT TRUNCATED AT 250 WORDS)     

EB virus antibody at different ages

In relation to the study of infectious mononucleosis a survey of the prevalence of antibody to EB virus was made on the sera of persons of varying age from several different areas in England by the indirect immunofluorescence technique. About half those tested were found to have acquired antibody by the age of 4 years and there was a further significant increase in the proportion of those positive between the ages of 15 and 24 years. The finding of seroconversion in two patients who developed infectious mononucleosis provides further support for an association between EB virus and this condition.     

CHARACTERIZATION OF THE BASIS FOR DIFFERENCES IN SERUM DBH ACTIVITY IN IMMATURE AND ADULT RATS BY USE OF HOMOLOGOUS ANTIBODY

Abstract– Rat serum dopamine-β-hydroxylase (DBH) activity decreased 5-7-fold between 15 and 60 days of age. Immunoprecipitation performed with homologous antibody (guinea-pig anti-rat adrenal DBH) showed that during this time period the quantity of antibody necessary to precipitate 50% of the enzymatic activity (AD₅₀) decreased 5-fold from 0.25 to 0.05 μl/ml. The biochemical properties of rat serum DBH at 15 and 60 days of age were compared to test the hypothesis that there might be different biochemical forms of the enzyme in the blood of immature and adult rats. Thermal stability, apparent K_m for tyramine, electrophoretic mobility, pH optima and elution profile on gel filtratioh chromatography were all found to be similar for rat serum DBH at both ages. On the basis of homospecific activity and multiple similarities in biochemical characteristics, it appears that differences in serum activity at the two ages reflect differences in the steady-state levels of enzyme. To determine the turnover of serum DBH in the two age groups, the recovery of enzyme activity was monitored after acute clearance of the circulating pool of DBH by treatment with the homologous antiserum. Immunotitration of DBH activity in vivo indicated that the total pool of serum enzyme was 4-fold greater in the mature rat than in 4-day-olds. After treatment of adult rats with 2μl of homologous antiserum, serum DBH activity was reduced by 85% with a half-life of recovery of 3.0 ± 0.6 days; the estimated fractional rate of degradation was 0.23 ± 0.06 day^?1 and the rate of entrance was 2.3 ± 0.2 units/ml/day. After treatment of 4-day-old rats with 1 μl of homologous antiserum, serum DBH activity was reduced by 95% with a half-life of recovery of 3.3 ± 0.5 days: the estimated average fractional rate of degradation was 0.22 ± 0.06 day^?1 and the average rate of entrance was 10.7 ± 1.6 units/ml/day. Thus, the several-fold difference in steady-state levels of serum DBH in rat pups as compared to adult rats appears to be due to greatly increased rates of entrance of the enzyme in the immature rats.