Specific prevention of diphtheria in adults in foci of this infection

The studies demonstrated the immunological and epidemiological effectiveness of a single injection of adsorbed diphtheria-tetanus toxoid with reduced antigen content for adults: intense antidiphtheria immunity in 92.3% of the vaccinees 1-3 months and in 94.5% of the vaccinees 1 year after the injection. This immunity remained sufficiently intense for 3 years (the term of observation). The geometric mean of antitoxic titers was 0.84 I. U./ml. The highest intensity of immunity appearing after the injection was observed in persons aged 18-20 years who showed the highest antitoxic titers (exceeding 0.5 I. U./ml) in 100% of cases, the lowest intensity was registered in the age group of 30-39 years; in 14.2% of these vaccinees antitoxic titers were below the protective level. In other age groups (40-49 years, 50 years and over) the intensity of immunity was high. The geometric mean of the titers of diphtheria antitoxin were 1.2 I. U./ml and 2.1 I. U./ml respectively. In none of the foci under study the spread of the manifest forms of the disease was observed.     

Enhancement of antitoxic immunity in newborn infants by peroral administration of donor antistaphylococcal immunoglobulin

The possibility of enhancing specific immunity by the oral administration of homologous antistaphylococcal immunoglobulin in a dose of 50 I. U./kg b. w. before the first feeding was shown in 75 newborn infants with a high risk of staphylococcal infection. 24 hours after the first administration of Ig the titer of staphylococcal anti-alpha toxin in the blood rose from 0.68 +/- 0.05 I. U./ml to 2.9 +/- 0.14 I. U/ml, on day 7 this titer persisted at the level of 2.86 +/- 0.12 I. U./ml, and 3 months later the titer was 1.5 +/- 0.05 I. U./ml. No side effects were observed. In the reference group (50 infants) antitoxic titers remained low. No suppurative-septic diseases were observed in the test group within 3 months, while in the controls, focal forms of staphylococcal infection (12 cases) and sepsis (1 case) were registered.     

Evaluation of the anti-rubella immunity levels on a lot of 5,000 sera from women at procreative age, tested by HAI, in Romania

From the study performed on a lot of 5030 sera, prelevated from women between 15-40 years old, tested by hemagglutination inhibition reaction (HAI), divided in 5 age groups of 5 years each, resulted that the percentage of women that can be considered immunologically protected against rubella (with HAI antibody titers greater than or equal to 1/20) varied between 79.5% (15-20 years of age group), and 75.3% (31-35 years of age group). The average percentage for the total lot was 76.7. The geometrical means (MGx/divided by SG) of the individual HAI titers ranged between extreme values of 54.2 (x/divided by 4.1) for the Group I, and 40.7 (x/divided by 3.8) for the Group IV, presenting the value of 44.4 (x/divided by 3.9) for the total lot. The covering coefficients of the protection limit, estimated at the level of geometrical means of antibody titers, ranged between 2.7 and 2.0, according to the age group, while the estimations made at the levels of the limits of the statistical range of one geometric standard deviation (MG x/divided by SG), presented values comprised between 11-8 and 0.7-0.5, respectively. On the basis of some theoretical mathematical models proposed in the literature (and using data resulted from the study performed), an attempt was made to approximate the rate of fetal exposure as well as the presumptive risk of congenital rubella syndrome (to 0/0000 live-born).     

Transplacental antibodies. Part II: Maternal antibodies against the toxins of C. diphtheriae and C. tetani

Examinations of 297 sera for diphtheria antitoxin and 160 sera for tetanus antitoxin were carried out in 1981. All sera were obtained from the cord blood of mothers between 15 and 34 years of age. The mothers were divided into four age groups each of which was further subdivided into the primipara and multipara subgroups. The aim was to assess the age-specific variations in response to active immunization against diphtheria and tetanus. The protective level of diphtheria antitoxin (at least 0.01 I.U./ml) was recorded in the serum of 96.3% of examinees and the rates of seropositivity were found to fall with increasing age. The protective level of tetanus antitoxin (at least 0.1 I.U./ml) was found in the serum of 95.2% of mothers. The serologic response encountered in groups of older mothers was a clear-cut demonstration that the country-wide mass immunization against tetanus carried out between 1974 and 1975 was highly effective and fully justified. The variations in the diphtheria and tetanus antitoxin levels found in the primipara and multipara subgroups were not statistically significant.     

The immunological efficacy of one, two and three inoculations against diphtheria in adults

The outbreak of diphtheria in the Republic of Belarus developed in the presence of a sharp deficiency of immunity among the population aged 35 years and over. In connection with a higher initial immunity level resulting from vaccination made in one injection the minimum antibody level (> or = 0.01 I.U./ml) was found in 79.7% of the examinees among the population under 35 years. For the age group of 35-60 years vaccination in one and two injections proved to be insufficiently effective (the minimum protective antibody titer was found, respectively, in 64.3% and 63.3% of the vaccinees). To achieve the full protection of this group of the population, vaccination in three injections was necessary; after that the minimum protective antibody titer was found in 90.7%, the protective antibody titer (0.1 I.U./ml) was found in 53.5% and the highly protective antibody titer (1.0 I.U./ml) was found in 11.6% of the examinees. The low level of highly protected persons among vaccinees receiving three injections was due to a low dose of diphtheria toxoid (2 Lf) in adsorbed DT-m vaccine with reduced antigen content.     

Antityphoid and antitetanic intradermal vaccination of chronic neuropsychic patients in a typhoid fever outbreak.

Intradermal immunization of 229 chronic neuropsychic patients in Gura Ocnitzei Sanatorium, D?mbovitza County, where a typhoid fever outbreak burst, was performed with a freeze-dried typhoid vaccine, suspended in purified and concentrated tetanic anatoxin. Adverse reactions were minimal and immunologic response, evaluated by laboratory tests, was good, reaching the level of that obtained as a result of classic vaccination methods (subcutaneous antityphoid and intramuscular anti-tetanic). Both after vaccination and also booster O and H agglutinating titers increased 4-7 times and anti-S. typhi. seroprotecting effect reached and maintained a high level. Moreover, antityphoid vaccination permitted epidemic focus limiting and its complete extinguishing after booster. Antitetanic vaccination resulted in protecting titers settlement (greater than or equal to 0.01 IU/ml) in all previously non-protected persons (1/3 of all subjects) and in the increase of protecting titers, existing before vaccination in the other persons.     

Evaluation of rabies virus neutralizing antibody titres induced by intramuscular inoculation of rabies DNA vaccine in mice and Bonnet monkeys (Macaca radiata)

A rabies DNA vaccine consisting of plasmid DNA expressing the rabies virus surface glycoprotein was injected (im) twice at two week interval to outbred swiss mice or Bonnet monkeys (Macaca radiata) and the levels of rabies virus neutralizing antibody (VNA) titres were examined over a one year period. In mice, the VNA titre was maintained above the minimum protective level (0.5 I.U./ml) up to 10 months after primary immunization, while in monkeys, the titre dropped below the protective level by 6 months. An anamnestic B cell response was seen in both mice and monkeys following the administration of a booster dose, 10 and 6 months after the primary immunization, respectively. These results indicate that im injection of rabies DNA vaccine induces VNA in nonhuman primates and mice unlike intradermal (id) immunization, which was shown to induce VNA only in mice but not in monkeys. This is the first report on the induction of VNA in nonhuman primates by im inoculation of rabies DNA vaccine.     

Survival of Enterobacter cloacae and Pseudomonas paucimobilis in yoghurts manufactured from cow's milk and soymilk during storage at different temperatures.

The survival of two microbial contaminants, Enterobacter cloacae and Pseudomonas paucimobilis, in yoghurts manufactured from cow's milk and soymilk was investigated during storage for 45 days at 4 and 12 degrees C. Sensory panel tests performed before microbiological investigation, showed that the flavor of soy-yoghurts made with cocoa powder or malt added did not have the beany taste of soy beans. Both contaminants were significantly resistant to low pH values during storage for 32 days at 4 degrees C. The survival at 4 degrees C was remarkable in both plain and flavored yoghurts and a population close to 10(2) C.F.U./ml was observed after 38 days of storage. Experiments performed with soymilk yoghurts showed an enhanced survival of P. paucimobilis at 4 degrees C compared to the storage in cow's milk yoghurts; microbial values were close to 7-8 x 10(6) C.F.U./ml after 16 days. Soymilk exhibited a protective effect on L. delbrueckii subsp. bulgaricus and S. thermophilus at 12 degrees C and, compared to the survival in cow's milk yoghurts, a larger number of viable cells of both probiotic microorganisms (10(6) and 10(8) C.F.U./ml, respectively) were observed after 36 days of storage.     

国产甲型肝炎灭活疫苗用于儿童免疫效果研究

为了探讨国产甲型肝炎灭活疫苗在儿童中应用的免疫效果,选择2～15岁抗-HAV阴性健康易感儿童91名作为接种对象,采用0、6程序接种国产甲型肝炎灭活疫苗250U／剂,观察免疫后的局部反应和全身反应,并于全程免疫后一个月检测抗-HAV阳转率和抗体GMT。结果91例观察对象在初免和加强免疫后均未见即时副反应,只在8～72小时内出现轻微的一过性局部和全身反应。全程免疫后一个月抗-HAV阳转率为100％。抗体GMT为14 407mIU／ml。国产甲肝灭活疫苗在儿童中应用具有良好的安全性和免疫原性,采用0、6个月程序可获得高滴度抗体。     

The creation of specific immunity to staphylococcal infection in newborn infants by the intranasal administration of adsorbed staphylococcal anatoxin

The possibility of enhancing specific immunity in newborn infants by the intranasal administration of adsorbed staphylococcal toxoid to infants with a high risk of staphylococcal infection in doses of 1 drop (0.05 ml) into each nostril during the first 7-9 years of their life. On days 7-9 the level of anti-alpha-toxin in the blood rose to 3.8 +/- 0.14 I. U./ml and remained sufficiently high 3-6 months later. When this method was used for the simultaneous immunization of mothers, their antitoxic titers were not as high as in newborn infants. No side effects were observed. In the control group, the titers of anti-alpha-toxin were low during the whole period of observation. Infants immunized by the proposed method had no staphylococcal infections both during the newborn period and within the first year of their life. In the control group, 8 cases of minor forms of purulent septic infection were registered during the newborn period, and in 2 infants umbilical staphylococcal sepsis was diagnosed.     

Epidemiological and immunological features of tetanus under conditions of long-term planned vaccine prophylaxis

The introduction of mass immunization against tetanus has resulted in the decrease of morbidity rate (5.2 times), the leveling of morbidity rate among the urban and rural population and among males and females, though no essential effect on the seasonal distribution of tetanus morbidity has been observed. Persons over 50 years of age (housewives and pensioners) have become the main groups of risk at the post-immunization period. Mass immunization against tetanus over a period of many years has ensured the existence of a sufficient immune stratum (89.9 +/- 3.0% to 100 +/- 3.0%) and a sufficient level of antitoxic immunity (means geom equal to 6.72-9.6 I.U./ml) among children. Among adults, the proportion of persons protected from tetanus decreases in older age groups from 82.1 +/- 1.3% in persons aged 31-40 years to 22.1 +/- 2.0% in persons over 60 years. The observed differences between the coverage of the population with immunization and the proportion of persons having protective titers of tetanus antibodies require constant control of the intensity of immunity and its correction with regard to its initial level, especially in persons of older age groups.     

Idiopathic central precocious puberty in girls as a model of the effect of plasma estradiol level on growth, skeletal maturation and plasma insulin-like growth factor I

Girls suffering from idiopathic central precocious puberty (CPP) may have different levels of estrogenic activity. This study was performed to evaluate the relationship between the estrogenic activity and the hypothalamopituitary activation and the effect of various plasma estradiol (E2) levels on growth, skeletal maturation and plasma insulin-like growth factor I (IGF-I). Fifty-eight girls with CPP were divided into 2 groups: group I with E2 less than 25 pg/ml (13 +/- 1 pg/ml, mean +/- SEM, n = 26) and group II with E2 greater than or equal to 25 pg/ml (52 +/- 3 pg/ml, n = 32). The mean ages at onset and at evaluation were lower in group I (5.9 +/- 0.4 and 6.8 +/- 0.4 years) than in group II (6.8 +/- 0.3 and 8.1 +/- 0.2 years, p less than 0.01), but the durations since onset (greater than 0.5 and less than 2 years) in the two groups were similar. The mean peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios were lower in group I (0.8 +/- 0.2) than in group II (1.7 +/- 0.2, p less than 0.001) and correlated with E2 (r = 0.41, p less than 0.01). The mean height gains during the year preceding the initial evaluation were similar in the two groups (8.7 +/- 0.5 vs. 9.2 +/- 0.4 cm). They were independent of the plasma E2 level. Conversely, the mean plasma IGF-I values were lower in group I (2.4 +/- 0.3 U/ml) than in group II (4.2 +/- 0.6 U/ml, p less than 0.01) and correlated with E2 (r = 0.52, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantification of plasma-derived blood coagulation factor VIII by real-time biosensor measurements

Plasma-derived blood coagulation factor VIII was analyzed in real time using biosensor technology. Monoclonal antibodies directed against the heavy and against the light chain of factor VIII were immobilized on different carboxymethyl dextran surfaces. Different factor VIII concentrations were injected over the antibody surfaces in parallel and response levels were determined from the dissociation phase at a fixed time after sample injection. Serial dilutions of plasma-derived factor VIII with known concentrations determined by a commercial FVIIIC:Ag ELISA were used as standards. A quantification limit of 0.9 I.U./ml with antibody 530p and 1.5 I.U./ml with antibody 531p was calculated. Intra-assay precision expressed as percent coefficient of variation was below 10% for concentrations above 0.6 I.U./ml. Inter-assay precision for antibody 530p was below 20% for concentrations higher than 0.6 I.U./ml. For 531p, inter-assay precision was below 10% for concentrations higher than 2 I.U./ml. A sensor chip lifetime in respect to regeneration of at least 100 cycles for both antibodies was found. The small sample requirement of 35 μl allows fast analysis of different FVIII products and the use of two monoclonal antibodies directed against two different FVIII domains provides additional information about the integrity of the FVIII molecule.     

Characteristics of the immune response to staphylococcal anatoxin in healthy persons

The immunization of young healthy males with adsorbed staphylococcal toxoid revealed the existence of two main types of postimmunization humoral response. One of them was characterized by an early (on days 7-14 after immunization) rise in the titer of antibodies with the subsequent gradual decrease of their content, while the number of circulating T-suppressors remained unchanged. The characteristic feature of the other type was a slow rise in the level of antitoxins by day 21 after immunization with the subsequent drop of their titers, preceded by a considerable increase in the number of circulating T-suppressors. The maximum antibody titer was definitely higher in the first type of response than in the second type (14.8 +/- 1.41 and 9.0 +/- 1.53 I. U./ml respectively). A single plasmapheresis procedure on day 21 after immunization produced no essential effect on the dynamics of the characteristics of cell-mediated and humoral immunity.     

The coagglutination reaction for detecting diphtheria toxin

High-titer antidiphtheria antitoxic rabbit serum has been obtained, and on the basis of this serum a coagglutinating diagnosticum has been developed. The sensitivity of the test has been found to depend on the content of antitoxic antibodies in the serum and on its purity. Diagnostica prepared from native serum containing 500 I. U./ml (a titer of 1:51, 200 in the passive hemagglutination test) permit the detection of 0.02-0.03 Lf/ml of diphtheria toxin. A decrease in antibody titer to 5-25 I. U./ml leads to a drop in sensitivity to 0.2-2 Lf/ml. The use of LgG fraction and pure antibodies increases the sensitivity of the test to 0.002-0.003 Lf/ml. The possibility of detecting toxin in Corynebacterium diphtheriae strains is shown.     

Effectiveness of immunizing donors with adsorbed tetanus anatoxin in relation to their genetic markers

Blood groups, including rhesus grouping, have been determined in 218 donors and HLA of loci A, B, C in 121 donors immunized with adsorbed tetanus toxoid (40 binding units). The presence of HLA Aw 32, B 8; HLA Bw 16, haplotypes A3 Bw 16 and A1, blank antigens of locus C is linked with the production of, respectively, high or low (less than or equal to 16 I.U./ml) antibody titers. The effectiveness of immunization is influenced by agglutinogen B, which is confirmed by its associations (in a complex with HLA Bw 16 or Bw 35) with low immune response.     

A new method to efficiently produce transgenic embryos and mice from low-titer lentiviral vectors

Vector injection into the perivitelline space has emerged as the standard delivery method to transduce lentivirus to mammalian oocytes or one-cell embryos, but its application is limited by the need for high titers of lentivirus. Herein we developed a new method by using a Piezo impact micro-manipulator for injecting low titer of lentivirus into the subzonal space of two-cell embryos or the perivitelline space of one-cell embryos that were shrunk with a highly concentrated sucrose solution. The survival rate of embryos was greater than 98% using this micromanipulation strategy, which was increased compared to the normal one-cell embryo injection method. More than 90% of injected embryos were GFP positive after subzonal injection of a lentivirus vector carrying the GFP gene with titers of 2 × 10⁸ I.U./ml. Even when a low titer of lentivirus (2 × 10⁶ I.U./ml) was used, 53.26% and 40.85% transgenic embryos were obtained after two-cell embryonic injection and one-cell sucrose treated embryonic injection, respectively. The GFP-positive rates were also greater than in the conventional method of injecting one-cell embryos (25.39%). In addition, blastocysts from the two-cell embryo injection group displayed stronger GFP fluorescence than the one-cell embryo injection groups treated with or without the sucrose solution. Increased expression of GFP suggests that the embryos obtained from this injection method have higher exogenous gene expression levels compared to previous methods. Therefore, in contrast with the traditional injection method, we have demonstrated a simplified and efficient lentivirus-mediated gene transfer method based on a low-titer virus preparation.     

Temporal profiles of juvenile hormone titers and egg production in virgin and mated females of Heliothis virescens (Noctuidae)

Juvenile hormones (JH) I, II, and III were monitored in hemolymph of virgin and mated females of various ages in Heliothis virescens. JH I was the predominant homologue followed by JH II, but JH II was present at a higher level in young virgin females. JH III was detectable only at a low level. In virgin females, hemolymph JH titers were low at emergence (2.2ng/ml-total amount of JH I and JH II), but increased thereafter and reached a maximum at 24h of age (53.5ng/ml). At 30h and 36h of age, JH titers dropped to a low level, but increased again in older virgin females. After mating, JH titers increased significantly. JH titers at 0h after uncoupling (137.4ng/ml) were nearly 3 times as high as those in 24-h-old virgin females. Within 6h after uncoupling, JH titers decreased slightly, but titers increased with age of mated females and reached a level of 320.2ng/ml hemolymph at 72h after uncoupling. The titer of JH I and JH II was correlated highly with total number of eggs produced (r(2)=0.70, P<0.001). Mating stimulated JH production, resulting in an increase in egg production.     

Enhanced proliferation and progesterone production by porcine granulosa cells cultured with pseudorabies virus growth factor (PRGF).

The objective of this research was to study possible interactions of pseudorabies virus growth factor (PRGF) with ovarian tissue. Granulosa cells isolated from porcine ovaries were cultured as monolayers for 6 days in a control medium without PRGF and in medium supplemented with different doses of this agent. Increased population density and change towards more fibroblastic-like shape of cells cultured with 10(9) I.U PRGF was observed when compared with control culture. The cells divided significantly faster during 6 days of culture under the influence of 10(3), 10(4), 10(5), 10(6), 10(7), 10(8) and 10(9) I.U./ml of PRGF at a dose dependent manner. PRGF in a dose 10(9) I.U. added to cultured cells isolated from small and medium follicles did not influence progesterone secretion . An increase of progesterone secretion under the influence of PRGF in all investigated days of cultures was observed in cells isolated from large preovulatory follicles. The marked increase in progesterone content in PRGF treated culture in doses of 0.5x10(7), 0.5x10(8), 0.5x10(9) I.U. was observed during 4 and 6 days of culture. The rise of progesterone content was not connected with increased number of secretory cells, but with a stimulation of production per cell. PRGF exerted no visible effect on progesterone secretion by granulosa cells from small and medium follicles cultured for 6 days. The presented in vitro data provide evidence for a local action of PRGF in the follicle depending on the stage of follicular development and duration of exposure. Precise relevance of the interaction of PRGF with follicular development requires further study.     

Calcemic responses of Varanus flavescens to prolactin administration

The daily intraperitoneal injections of ovine prolactin to Varanus flavescens (10 I.U./0.2 ml/100 g body wt for 7 days) induced a rise in serum calcium which persisted until the end of the experiment.