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Biomedical subjects

J Nagel

Publications and source records attributed to J Nagel.

At least 55 records · Page 3Linked to original sources

Development of erythroid colony-forming cells in rat fetal spleen: apparent lack of sensitivity to an in vivo corticosteroid excess as compared to fetal liver.

The development of splenic erythroid colony-forming cells from rat embryos in the last 4 days of intrauterine life was examined after 2 and 7 days in a methylcellulose culture system. The number of 2- and 7-day erythroid colonies decreased sharply between, respectively, days 20 and 21 of gestation and days 19 and 20. Concomitantly, a maturation of proerythroblasts and basophilic erythroblasts to mature erythroblasts was detected on smears of splenic cellular suspensions. The effect of a corticosteroid excess induced by a maternal laparotomy was tested on spleen and liver cultures from the same control or experimental fetuses. The ratio of the number of 2-day to the number of 7-day erythroid colonies did not differ in experimental and control splenic cultures, but in liver cultures was significantly lower at days 19 and 20 in experimental than in control cultures.

Adrenal Cortex Hormones↗

Identification of neuropeptides in pelvic and pudendal nerve afferent pathways to the sacral spinal cord of the cat.

The distribution of several neuropeptides, including vasoactive intestinal polypeptide (VIP), substance P, somatostatin, leucine enkephalin, methionine enkephalin, and cholecystokinin, in sacral afferent pathways of the cat was examined by immunohistochemical techniques. Certain peptides (substance P, somatostatin, and leucine enkephalin) could be demonstrated in normal dorsal root ganglion cells; however, topical administration or injections of colchicine solution into ganglia 36-56 hours prior to removal markedly increased the number of cells labeled and the intensity of staining. Other peptides (VIP, cholecystokinin, and methionine enkephalin) were only detected in significant numbers of cells following intraganglionic injections of colchicine. The distribution of peptides in dorsal root ganglion cells projecting to the pelvic nerve (visceral) and the pudendal nerve (somatic) was examined by retrograde dye labeling combined with immunohistochemistry. Fluorescent dyes were applied to the cut ends of the nerves 2 weeks prior to removal. A considerably higher percentage of pelvic nerve afferent neurons than pudendal nerve afferent neurons exhibited peptide immunoreactivity; e.g., VIP (42% vs. 10%), cholecystokinin (29% vs. 12%), substance P (24% vs. 21%), leucine enkephalin (30% vs. 24%), and methionine enkephalin (10% vs. 3%). Somatostatin was present in only a small percentage of either type of afferent neuron (0.3-2%). The total percentage of peptide-containing pelvic afferent neurons exceeded 100% (137%), suggesting that more than one peptide is present in some visceral afferent neurons. This has been confirmed in preliminary experiments. The peptide-containing cells were in general less than 40 micron in average diameter; however, a significant percentage of substance P and cholecystokinin neurons ranged from 40 to 60 micron in average diameter. VIP cells had the smallest average diameter (30 micron) whereas somatostatin cells had the largest average diameter (36 micron). Statistical analysis of cell sizes revealed that substance P cells projecting to the pelvic nerve were smaller than substance P cells sending axons into the pudendal nerve. On the other hand, VIP cells in the two afferent pathways were not significantly different in size. Sacral visceral and somatic afferent neurons contain a wide spectrum of neuropeptides, some of which (e.g., VIP and cholecystokinin) seem to be preferentially distributed in the visceral afferent systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

New diagnostic and technical aspects of fetal phonocardiography.

A new generation of instruments designed to record the fetal phonocardiogram is discussed, as are new methods of time-domain and frequency-domain processing of the fetal phonocardiogram. Using these techniques, detailed information can be obtained about both fetal and maternal cardiovascular conditions.

Cardiovascular Diseases↗

Complementary DNA cloning and expression of the papaya ringspot potyvirus sequences encoding capsid protein and a nuclear inclusion-like protein in Escherichia coli.

Three cDNA clones that express viral gene products in Escherichia coli JM83 were derived from a watermelon mosaic virus-1 strain of papaya ringspot virus (PRSV-W). DNAs complementary to portions of the viral RNA were inserted into the pUC8 and pUC9 plasmids, and the expressed polypeptides were fusion products with the amino terminus of beta-galactosidase. Clones W1-77 and W2-1 expressed fusion products with apparent molecular weights of 40,000 (40K) and 14K, respectively, which were serologically related to PRSV capsid protein. A 52K product serologically related to a 54K nuclear inclusion protein of tobacco etch virus was produced by clone W1-18. The sequences encoding the capsid and 57K nuclear inclusion-like proteins of PRSV were physically mapped to adjacent positions through Southern blot analyses of clones W1-77 and W1-18.

Capsid↗

Vaccines and immunization schedules.

A simplified schedule, applicable in developing countries, has been tested for diphtheria, tetanus and pertussis (DTP) and polio immunization. It comprised two injections, six months apart starting at the age of 3 to 8 months. DTP and inactivated polio (IPV) vaccines of special composition and live measles vaccine given at the age of 9 to 14 months induced a good antibody response. Special attention is being given to pertussis immunity. Although low agglutination titers may sometimes be found, DTP vaccination was shown to interrupt the normal periodicity of pertussis epidemics. From the relatively high proportion of vaccines which attained pertussis specific serum IgA antibodies in the course of four years following vaccination, it could be deduced that vaccination does not prevent infection although it protects against disease. Based on these results, successful immunization against seven diseases will be possible in two sessions; DTP, IPV, and BCG vaccinations at the age of 3 to 8 months; and DTP, IPV, measles and yellow fever vaccination at the age of 9 to 14 months.

Adolescent↗

Improved serodiagnosis of whooping cough caused by Bordetella pertussis by determination of IgG anti-LPF antibody levels.

The enzyme-linked immunosorbent assay (ELISA) has been used for the determination of the isotype and the specificity of Bordetella pertussis serum antibodies induced by natural infection and by vaccination. In a previous study (J. Med. Microbiol., 16, 417-426 (1984)) it was shown that the presence of pertussis serum IgA antibodies could be used as an indicator of infection: IgA antibodies were not induced by vaccination nor transported from the mother to the serum of the child. In the present study ELISA was used for the determination of IgA, IgM and IgG antibodies. From the results obtained with sera from suspected pertussis cases, it was concluded that antibodies against FHA are hardly induced by infection, in contrast to anti-LPF (determined in a fetuin sandwich ELISA) and anti-LPS antibodies. In view of the lower standard deviation of the mean anti-LPF antibody titer these antibodies were studied more extensively. From a number of bacteriologically proved pertussis cases, it was shown that high levels of IgG anti-LPF antibodies were found before IgA antibodies could be detected. On the other hand, we had the impression that IgG antibodies declined more rapidly than IgA antibodies. One has, however, to take into account that IgG antibodies are transferred from mother to child. From assay of sera from infants prior to, during and two months after vaccination (ages of vaccination: 3, 4, 5 and 12 months) it was concluded that IgG anti-LPF antibodies were induced to a much lower level by DTP-polio vaccination (10 O.U. per dose) than by natural infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Development of individual insulin infusion profiles for open loop infusion systems.

A computer controlled syringe-type insulin infusion pump storing up to 254 different infusion rates, eight different meal programs and two different basal rates automatically changeable during 24 h in EPROM was used for insulin infusion applying a wavy step profile. This profile approaching the physiological postprandial insulin secretion of the B-cell was calculated by an algorithm following the biphasic insulin secretion model proposed by E. Cerasi . The computer program for the open loop infusion device simulated the feed-back structure of a closed loop insulin secretion control by an algorithm based upon a theoretical postprandial blood sugar profile. Fifteen unstable juvenile onset insulin requiring diabetics could be well controlled after two to three days of an intravenous open loop insulin infusion program. The programs consisted of two constant basal rates and superimposed wavy step profile programs activated at the beginning of each meal. The preabsorptive bolus or cephalic phase was an additional tool both for improved postprandial blood sugar control and further reduction of insulin consumption. The programmable insulin infusion device proved as a valuable tool for the study of a sophisticated insulin infusion profile suitable as well for open loop as for closed loop insulin infusion systems.

Adult↗

Comparison of ELISA and toxin neutralization for the determination of tetanus antibodies.

In a sandwich ELISA for tetanus antibodies, the influence of the tetanus toxoid concentration used for coating microtiter plates has been studied. The antibody levels by toxin neutralization bioassay and by ELISA were studied for a population with known immunization history. By decreasing the tetanus toxoid concentration in ELISA from 5 to 0.2 Lf/ml, a better correlation was found between the ELISA results and the bioassay titers, but sera from recently immunized people still showed high ELISA titers. This phenomenon cannot be ascribed to nonspecific reactions since sera from nonimmunized people are negative in both assays. All sera negative in ELISA had, however, a bioassay titer beneath 0.01 IU/ml.

Antibody Affinity↗

Serum erythropoietic activity in the rat around birth.

Using a fetal rat liver cell bioassay, serum erythropoietic activity was tested in non-suckled newborn rats comparatively to 21-day-old rat fetuses at time 0 or after 2 h of surviving. The number of erythroid colonies (CFUe) is significantly greater in cultures with neonatal and fetal rat serum after 2 h of surviving than in cultures with fetal rat serum sampled at time 0. These results suggest a release of erythropoietin or erythropoietin-like substances in response to a short hypoxic phase following the parting of the fetus with the mother and preceding the autonomous oxygenation of the newborn by breathing.

Animals↗

The influence of malaria and gestation on the immune response to one and two doses of adsorbed tetanus toxoid in pregnancy.

The effect of Plasmodium falciparum infection on the response to immunization with tetanus toxoid in pregnancy is of importance because malaria is more frequent and severe in pregnant women. This paper presents the results of a study in west Kenya of the antibody response to an adsorbed tetanus toxoid in primigravidae and multigravidae living under holoendemic conditions. There was no apparent influence of either P. falciparum infection or gestational age on the immune response to one and two doses of adsorbed toxoid. The antibody response in pregnant women with and without malaria was comparable to that in non-pregnant healthy adults. Previous studies of responses to primary immunization schedules in pregnant and non-pregnant women are reviewed.

Antibody Formation↗

A modified ELISA technique for the titration of antibodies to polio virus as an alternative to a virus neutralization test.

An ELISA based on inhibition of antibody binding for the determination of antibodies to polio virus type I is described. F(ab1)2-fragments of bovine antibodies to polio virus type I are used as the capture antibody thus lowering the background staining. A good correlation was found between the poliovirus neutralizing antibody level and the antibody titers as determined by ELISA.

Animals↗

The enzyme-linked immunosorbent assay of meningococcal and some related Escherichia coli polysaccharides.

A non-competitive enzyme-linked immunosorbent assay (ELISA) system has been developed for the quantitative, sensitive and specific determination of meningococcal polysaccharides. A prerequisite, however, is the correspondence of the O-acetyl content and the molecular size of the polysaccharides in the samples and the reference preparation. If these characteristics differ, special precautions in the use of antibodies to both the O-acetylated and the non-O-acetylated variants have to be taken, including the testing of the sample in at no less than three dilutions.

Antigens, Bacterial↗

Vaccine potential of meningococcal group C polysaccharide-tetanus toxoid conjugate.

The antibody response in mice to Neisseria meningitidis (meningococcal) group C polysaccharide could be modified by its conjugation to proteins, i.e. tetanus toxoid. Whereas the pure polysaccharide behaved as a T-independent antigen, the polysaccharide-protein conjugate was clearly a T-dependent antigen, as shown by the pronounced IgG response after the first dose and by the booster effect after the second dose. In comparison, group C polysaccharide-outer membrane protein complexes isolated from the cell-free culture liquid of a meningococcal culture induced only a low level of IgG antibodies. Conjugation did not result in a reversion of tetanus toxoid to toxin. Tetanus toxoid present in the conjugate was as immunogenic as tetanus vaccine.

Animals↗

Serum IgA antibody to Bordetella pertussis as an indicator of infection.

The levels of pertussis-specific IgA antibodies in sera from vaccinees and from children with Bordetella pertussis infection were compared by an enzyme-linked immunosorbent assay (ELISA). Serum IgA antibodies were produced only after natural contact with the pathogen and, therefore, their presence can be used as an indicator of infection. However, in view of the relatively long interval between infection and the appearance of antibodies, and the prolonged antibody response, their presence cannot be used as proof of recent infection. The finding of these antibodies in a high percentage of the normal adult population may indicate a constant circulation of B. pertussis without symptoms of disease.

Adolescent↗

Immunological evaluation of meningococcal group C polysaccharide-tetanus toxoid conjugate in mice.

Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugate was prepared to obtain the polysaccharide component in a thymus-dependent form and to preserve the immunogenic properties of the tetanus toxoid component. Biochemical and immunochemical analyses of this conjugate revealed that (i) it was composed of equal amounts of polysaccharide and protein; (ii) the antigenic activity of the polysaccharide component was greatly reduced; (iii) it contained about 10% free polysaccharide; (iv) the composition was not homogeneous; and (v) only 5% of the tetanus toxoid component was present at the surface of the conjugate molecules. In this study, the influence of these characteristics on the antibody response to both components in mice was investigated. The dose-response relationship, the persistence of antibodies, a possible antigenic competition, and the specificities of the antibodies induced were also studied. Our data suggest that the conjugate behaves as a pronounced thymus-dependent antigen, that the tetanus toxoid component is more immunogenic at lower dosages (0.8 and 20 ng) than equivalent doses of tetanus vaccine, that the presence of free polysaccharide does not influence the induction of antibodies to polysaccharide by the conjugate, and that no antibodies to new structures in the conjugate are induced. These characteristics favor the application of this conjugate as a vaccine for human use.

Animals↗