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Biomedical subjects

M Gahr

Publications and source records attributed to M Gahr.

At least 73 records · Page 4Linked to original sources
PubMed1993

[Immunological principles of polysaccharide-protein conjugate vaccination].

Haemophilus influenzae and Streptococcus pneumoniae are bacteria with a polysaccharide capsule. The production of specific antibodies against capsular polysaccharide plays a pivotal role in the defence against these organisms. However, children under the age of two years do not at all or only poorly respond to an infection with encapsulated bacteria or after vaccination with purified capsular polysaccharide antigen. In contrast, protein antigens, e.g. tetanus- and diphtheriae-toxoid, are good immunogens in this age group. The difference between polysaccharide antigen and protein antigen is that the former are T-dependent antigens whereas the latter are T-independent. The reason for this age dependent "immunodeficiency" is not clear. A functional immaturity of a B-cell population seems to be the reason for the unresponsiveness of young children against Ti-2 antigens. The Haemophilus conjugate vaccine contains the capsular polysaccharide chemically conjugated to a carrier protein. This results in an immune response against the polysaccharide with characteristics of a T dependent antigen, giving high immunogenicity even in children under the age of two years, resulting in high antibody-production and the induction of immunological memory.

Antibodies, Bacterial↗
PubMed1993

Is the IFN-gamma-induced enhancement of superoxide production in CGD-phagocytes caused by increased expression of the p47-phox cytosolic protein.

Interferon-gamma (IFN-gamma) had been shown to increase superoxide production of cultured monocytes from patients with chronic granulomatous disease (CGD). To elucidate the mechanism of the IFN-gamma-induced improvement of superoxide production of cultured monocytes from patients with CGD we examined the influence of IFN-gamma on the expression and the activity of the NADPH-oxidase in the monocytic cell-line Mono Mac 6. After cultivation of Mono Mac 6-cells in the presence of 500 U/ml IFN-gamma the superoxide production was found to be increased as well as the expression of the p47-phox cytosolic protein of the phagocytic NADPH-oxidase.

Cell Line↗
PubMed1992

Development of a quasispecies of human immunodeficiency virus type 1 in vivo.

During treatment with one specific batch of blood clotting factor IX, a number of hemophilia B patients in Germany recently became infected with human immunodeficiency virus type 1 (HIV-1). The nucleotide sequences of cloned HIV-1 envelope gene regions including the variable V3 loop and the V4 region derived from short-term virus cultures and directly from peripheral blood cells of these patients were shown to be highly homologous. Based on the assumption that the corresponding consensus sequence (termed HIV-1MBK) was identical to the genotype of the initially infecting virus, we were able to construct phylogenetic trees of the developing quasispecies in two patients studied in detail. True intermediates between input and multiply mutated genotypes were found in individual blood samples. Except for the initially infecting variant HIV-1MBK, variants found at 11 months postinfection had replaced those seen at 5 months postinfection. Variability early after infection was shown to cluster in two small regions located 3' of the V3 loop (i.e., outside the loop) and within the V4 region. This communication therefore describes the evolution of an HIV-1 quasispecies in humans starting from a single genotype.

Amino Acid Sequence↗
PubMed1992

Modulation of human monocyte superoxide production by recombinant interleukin-3.

We have examined the generation of superoxide by human monocytes isolated from peripheral blood cultured in the presence of recombinant human interleukin-3 in comparison to tumor necrosis factor-alpha and interferon-gamma. The rate of superoxide production of unstimulated and stimulated monocytes [by formyl-methionyl-leucyl-phenylalanine (0.1 microM) and by phorbol-myristate-acetate (2 ng/ml and 200 ng/ml)] decreased during the culture period in the absence of interleukin-3, whereas cells treated with interleukin-3 maintained or surpassed their initial superoxide-producing capacity. An increase of phorbol-myristate-acetate- and formyl-methionyl-leucyl-phenylalanine-stimulated superoxide production of monocytes cultured with interleukin-3 compared to control cells was detected first after 24 h of monocyte culture. It was maximal after 96 h of monocyte culture. At this time the stimulated superoxide production of monocytes cultured in the presence of interleukin-3 surpassed that of interferon-gamma and tumor necrosis factor-alpha treated cells. Suboptimal concentrations of the stimulus phorbol-myristate-acetate (2 ng/ml) resulted in higher priming than 200 ng/ml phorbol-myristate-acetate. A dose dependence of the effect of interleukin-3 on the superoxide production was observed. Our results demonstrate that interleukin-3 primes cultured human peripheral blood monocytes for enhanced stimulated respiratory burst activity to a higher extent than interferon-gamma and tumor necrosis factor-alpha.

Cell Adhesion↗
PubMed1992

Prolactin and gonadal steroids during the reproductive cycle of the Bengalese finch (Lonchura striata var. domestica, Estrildidae), a nonseasonal breeder with biparental care.

Plasma levels of prolactin (Prl), testosterone (T), and progesterone were determined throughout the breeding cycle in pairwise caged Bengalese finches (Lonchura striata var. domestica, Estrildidae), a monogamous altricial passerine with nonseasonal breeding, in which parental behavior including incubation is equally shared between males and females. In both sexes, Prl titers increased 4- to 10-fold during incubation period compared to values during nestbuilding. Likewise, Prl levels after fledging of the young were significantly lower compared to titers during incubation. In males, T increased significantly (15-fold) during nestbuilding compared to all other stages of the breeding cycle. In females, T remained basal throughout the entire breeding cycle. Thus, T levels were elevated only during stages with low Prl titers and vice versa. Progesterone titers were elevated during egg-laying in females and fluctuated without any obvious pattern in males. These results suggest that (1) high levels of Prl are involved in the control of parental behavior of male and female Bengalese finches and (2) Prl secretion is controlled by proximate factors of the early reproductive cycle since reproduction is independent of seasonal factors in this species.

Animals↗
PubMed1992

Sites of estrogen uptake in embryonic Trachemys scripta, a turtle with temperature-dependent sex determination.

Female sex determination can be induced in embryonic red-eared slider turtles (Trachemys scripta) by exogenous estrogen, as well as by incubation at warm temperature. In the present study, estrogen target areas were identified in embryos before (stage 15), during (stage 18), and after (stage 22) the critical period for sex determination. Both hyperfilm and emulsion autoradiography were used to localize tritium accumulation after the injection of radiolabeled 17 beta-estradiol. Site-specific tritium-labelling was found at all stages, notably in the mesonephros at stage 15, in the mesonephros and oviduct at stage 18, and in the mesonephros, oviduct, and the interrenal gland at stage 22. Few if any cells in the gonad were tritium-labeled at any stage. The large number of estrogen-concentrating cells in the mesonephros and interrenal and the lack of binding to gonadal tissues indicates that estrogen action on gonadal differentiation during the period of sex determination may be indirect.

Animals↗
PubMed1992

Behavioral action of estrogen in the male dove brain: area differences in codistribution of aromatase activity and estrogen receptors are steroid-dependent.

Brain aromatization of androgen to estrogen (E) and presence of estrogen-receptor (ER) containing cells (ERC) are required for the control of E-dependent neural events under-lying male sexual behavior. We examined whether (a) numbers of ERC and steroid-inducible aromatase activity are codistributed and directly correlated in the same brain areas of individual sexually active male doves and whether, (b) distribution of ERC is altered by a change in E formation in preoptic areas known to be involved in control of male behavior. To allow spatial correlation between ERC and aromatase activity, a new approach was used that combined in vitro measurement of aromatase activity (stereospecific formation of 3H2O from [1 beta-3H]-testosterone) in microdissected brain areas of one side of the brain and immunocytochemical localization of ERC (ER antibody H222Spy) in homologous contralateral areas of the same coronal brain section. The relationship between ERC and aromatase activity differs according to brain area in sexually active males: (a) large populations of ERC in preoptic areas, notably in nucleus preopticus medialis (6.5 +/- 0.8 ERC/5,000 microns2) and nucleus preopticus medialis, pars medianis (9.5 +/- 1 ERC/5,000 microns2) are codistributed with high steroid-dependent aromatase activity (greater than 100 fmol/mg tissue); (b) areas containing the nucleus interstitialis and ventromedial hypothalamic nuclei also have relatively high aromatase activity, but lower ERC density than POA; (c) the anterior hypothalamic nuclei have few ERC, but steroid-regulated aromatase activity; (d) the infundibular area contains elevated ERC and little steroid-inducible aromatase activity; (e) area basalis and neostriatum contain few or no ERC and no inducible aromatase activity. Castration of sexually active doves reduces aromatase activity in preoptic and posterior hypothalamic areas (by greater than 75%) to basal levels, but does not affect the distribution or number of ERC in brain areas containing steroid-regulated aromatase activity, notably in the preoptic area. The results show that steroid regulation of aromatase occurs in brain loci with high numbers of ERC. We suggest that steroid-inducible aromatase occurs in brain loci with high numbers of ERC. We suggest that steroid-inducible aromatase activity and ERC are codistributed in areas controlling male sexual behavior; thus the formation and action of E may occur in the same area. Regulation of the aromatase activity and supply of E, but not of number of cells containing ER, is one mechanism which accounts for changes in action of testosterone on estrogen target sites in the male brain.

Animals↗
PubMed1992

[Kawasaki syndrome. Association with exposure to carpet shampoo and successful therapy with immunoglobulins in the second week of the illness].

A male infant and a three year old girl, both with acute febrile illness, were admitted to our hospital for suspected meningitis/sepsis and gastroenteritis/severe viral infection, respectively. Both showed all six principal features of Kawasaki syndrome and revealed several other symptoms and laboratory findings commonly associated with the disease. The infant had multiple coronary aneurysms. The girl developed ascites, pancreatitis and iritis, all of which are seldomly recognized symptoms of the Kawasaki syndrome. The prompt and satisfactory therapeutic responses of both patients to the combined therapy consisting of oral acetylsalicylic acid (50-100 mg/kg b.w./d) and intravenous gamma-globuline (400 mg/kg b.w./d) at the eight and even eleventh day of illness support the use of gamma-globuline therapy beyond the first week of the disease. Prior to their illnesses both children had been exposed to carpet shampoo, an agent which has been repeatedly associated with an increased risk of Kawasaki syndrome.

Aspirin↗
PubMed1991

Influence of lactoferrin on the function of human polymorphonuclear leukocytes and monocytes.

Polymorphonuclear leukocytes (PMN) exposed to highly purified human lactoferrin (from colostrum) exhibit an increased random motility (at least 2.5-fold) and are primed to produce more superoxide [12.1 +/- 1.2 nmol O2-/min/10(6) PMN preincubated with lactoferrin (0.5 mg/ml) against 6.4 +/- 2.3 with cells without lactoferrin after FMLP stimulation]. The action of lactoferrin seemed to be specific, because it could be abolished by simultaneous addition of antilactoferrin antibody. Addition of transferrin and iron salts to PMN was without effect. Between iron-poor and iron-saturated lactoferrin there was no difference in influence on PMN function except for a higher FMLP stimulated superoxide production by iron-saturated lactoferrin. Aggregation, degranulation (beta-glucuronidase, lysozyme), and bacterial killing were not influenced by lactoferrin. Incubation of monocytes and monocyte-derived macrophages with lactoferrin did not alter their motility or their superoxide production rates. Our findings indicate that PMN become more effective after exposure to lactoferrin by having a greater motility and producing superoxide at a faster rate.

Cell Aggregation↗
PubMed1991

Persistence of parvovirus B19-DNA in blood of a child with severe combined immunodeficiency associated with chronic pure red cell aplasia.

In a female child with severe combined immunodeficiency, pure red cell aplasia was observed which required regular transfusions of erythrocytes. Parvovirus B 19 DNA (but no antibodies) was detected in stored serum samples after the death of the patient. We suggest that the anaemia was a consequence of parvovirus infection which persisted for at least 2 years due to the immunodeficiency.

Chronic Disease↗
PubMed1991

Triosephosphate isomerase deficiency: haemolytic anaemia, myopathy with altered mitochondria and mental retardation due to a new variant with accelerated enzyme catabolism and diminished specific activity.

A new triosephosphate isomerase (TPI) variant is described in an 8-year-old Turkish girl suffering from chronic haemolytic anaemia, myopathy and developmental retardation since early infancy. The enzyme activity profile revealed a generalized deficiency in erythrocytes, granulocytes, mononuclear blood cells, skeletal muscle tissue and cerebrospinal fluid. The concentration of enzyme substrate dihydroxyacetone phosphate was distinctly elevated. Biochemical examination showed accelerated enzyme deamidation, the first step in the normal catabolism of TPI during aging of the erythrocyte. The specific activity of the variant TPI, determined by antibody titration, was reduced to 61% of normal. Its heat stability was markedly decreased. Muscle biopsy and neuropsychological testing further clarified the pathogenesis of the disorder. A prevalent alteration of mitochondria similar to that seen in mitochondrial myopathy and an elevated amount of intracellular glycogen were found. The patient's retarded intellectual development was mainly due to impaired visual perception and sensory-motor co-ordination in addition to a lack of syllogistic reasoning. The findings indicate that the low TPI activity leads to a metabolic block of the glycolytic pathway and hence to a generalized impairment of cellular energy supply.

Anemia, Hemolytic↗
PubMed1991

Cytokine secretion by peripheral blood monocytes from human immunodeficiency virus-infected patients is normal.

We have measured the production of interleukin 1 (IL 1), interleukin 6 (IL 6), and tumor necrosis factor alpha (TNF alpha) by unstimulated monocytes and monocytes stimulated with lipopolysaccharide (LPS) isolated from the peripheral blood of patients infected with human immunodeficiency virus 1 (HIV-1) and healthy controls. Spontaneous and LPS-induced cytokine production were not significantly different between patients and controls. Median lipopolysaccharide-stimulated cytokine secretion for patients and controls was 1.7 and 4.3 U/ml for IL 1, 475 and 625 U/ml for IL 6, and 468 and 580 pg/ml for TNF alpha. Cytokine levels were not related to stage of disease. We conclude that in vivo HIV infection itself does not alter peripheral blood monocyte cytokine secretion.

Adolescent↗
PubMed1991

Epidemiologically closely related viruses from hemophilia B patients display high homology in two hypervariable regions of the HIV-1 env gene.

The diversity of human immunodeficiency virus type 1 (HIV-1) is mainly caused by mutations that affect the gene encoding the gp120 envelope protein. Isolates differ to a large extent in the hypervariable regions of gp120. This study was undertaken to determine the degree of variation of HIV-1 env genes isolated from seven individuals with hemophilia B who became infected in association with administration of a suspected clotting factor lot. Two hypervariable regions and part of a constant region from proviral DNA of the peripheral blood leukocytes of these patients were amplified and the products of the polymerase chain reactions were sequenced. The sequences derived from five of the individuals displayed 100% sequence homology, 1 had two and 1 had six deviations from the consensus sequence. The alignment of the amino acid sequence so deduced revealed no comparable homology to any of these two hypervariable regions from a number of published isolates. The genetic variability of HIV-1 seems to be limited, at least in the early phase of infection, allowing the determination of close relationships between epidemiologically related strains.

Amino Acid Sequence↗
PubMed1991

Lack of HIV-1 V3 region sequence diversity in two haemophiliac patients infected with a putative biologic clone of HIV-1.

Peripheral blood mononuclear cells (PBMC) from two haemophilia B patients, who presumably became infected with a putative HIV-1 biological clone following treatment with the same suspected batch of commercial factor, were used to clone and sequence the hypervariable V3 region of the HIV-1 envelope protein. In 10 of 12 clones the V3 region was identical and two (one from each patient) had a single non-synonymous point mutation. Viable reisolates (shown to be authentic by sequencing of V3) currently appear to be monocyte tropic. These results strongly indicate that the patients were infected from a common source with a very low number of infectious particles and indicate that variability under these conditions is limited.

Amino Acid Sequence↗
PubMed1991

[LFA-1 defect: a rare granulocyte function disorders as a cause of therapy-resistant omphalitis in newborn infants].

A newborn infant suffered from severe omphalitis resistant to antibiotic therapy. The combination of the symptoms: delayed separation of the umbilical cord, omphalitis, impairment of wound-healing and extreme leukocytosis led to the diagnosis of LFA-1 (leukocyte function antigen)-deficiency, which was confirmed by monoclonal antibodies. The pathophysiology of this disorder is described shortly.

Anti-Bacterial Agents↗
PubMed1990

Delineation of a brain nucleus: comparisons of cytochemical, hodological, and cytoarchitectural views of the song control nucleus HVc of the adult canary.

The present investigation used stable area-specific, neuronal properties instead of Nissl stain to delineate the boundaries of the nucleus hyperstriatalis caudal c (HVc) in the telencephalon of the adult male canary. Immunocytochemical procedures combined with retrograde tracing labeled a large population of perennial long-projecting neurons that contain estrogen receptors in the canary HVc. The HVc area defined by the distribution of these neurons was congruent with the HVc area defined in Nissl-stained sections during the breeding period. The HVc area defined in Nissl-stained preparations showed an extensive seasonal change in size, confirming previous results (Nottebohm: Science, 214:1368-1370, '81). In contrast, the HVc area defined by the distribution of the estrogen receptor containing long-projection neurons showed little or no seasonal change in size. Because these neurons are permanent, the HVc seems to be of rather constant size year round. The internal morphology of the HVc, however, undergoes seasonal alterations, which are reflected in changes in size of the HVc area distinguishable in Nissl-stained sections. The combination of cytoarchitectural criteria of Nissl-stained preparations with area-specific cytochemical and hodological markers to delineate the boundaries of a brain nucleus might give new insights in the partitioning and neuronal plasticity of brain areas.

Animals↗
PubMed1990

Are separable aromatase systems involved in hormonal regulation of the male brain?

In vitro study of testosterone (T) metabolism shows that formation of estradiol-17 beta (E2) is regionally specific within the preoptic area (POA) of the male ring dove. The POA is known to be involved in the formation of E2 required for specific components of male sexual behavior. Two sub-areas of high aromatase activity, anterior (aPOA) and posterior preoptic (pPOA) areas, have been identified. Aromatase activity is higher in aPOA than in pPOA. The aromatase activity within the aPOA is also more sensitive to the inductive effects of low circulating T, derived from subcutaneous silastic implants, than the enzyme activity in pPOA. Kinetic analysis of preoptic fractions indicates that a similar high-affinity enzyme occurs in both areas (apparent Km less than 14 nM), but the Vmax of aPOA enzyme activity is higher than pPOA. Cells containing estrogen receptors (ER) are localized in areas of high aromatase activity. There is overlap between immunostained cells in the aPOA and in samples containing inducible aromatase activity measured in vitro. Within the aPOA there is a higher density of ER cells in the nucleus preopticus medialis. The pPOA area also contains ER, notably in the nucleus interstitialis, but at a lower density. We conclude that the hormonal regulation of the male preoptic-anterior hypothalamic region, which is a target for the behavioral action of T, involves at least two inducible aromatase systems with associated estrogen receptor cells.

Animals↗