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Biomedical subjects

M Gahr

Publications and source records attributed to M Gahr.

At least 55 records · Page 3Linked to original sources
PubMed1997

An in-frame triplet deletion within the gp91-phox gene in an adult X-linked chronic granulomatous disease patient with residual NADPH-oxidase activity.

In an adult patient suffering from X-linked chronic granulomatous disease (X-CGD) with residual activity of the NADPH-oxidase we found an unusual biochemical constellation with a defective gp91-phox gene. As shown by Western blot using a specific antibody the gp91-phox protein was normal in PMN. However, NADPH-oxidase activity was reduced and no heme spectrum was detectable. By Southern blot and RFLP analysis of genomic DNA a larger defect within the gp91-phox gene was excluded. Sequencing of the gp91-phox cDNA revealed an in-frame deletion of a TTC triplet in exon VI of the gp91-phox gene. This mutation indicates the loss of one amino acid (phenylalanine 215 or 216) in the gp91-phox protein. Sequencing of genomic DNA from the heterozygous daughter of the propositus confirmed this mutation. The absence of a functional cytochrome b558-spectrum in granulocytes of the patient suggests an involvement of the phenylalanine 216 area in heme binding by gp91 phox. This is the first mutation described in a X-CGD patient with absence of a functional cytochrome b558-spectrum but with detectable gp91-phox protein and residual NADPH-oxidase activity.

Adult↗
PubMed1997

Localization of androgen receptor mRNA-containing cells in avian respiratory-vocal nuclei: an in situ hybridization study.

Song development and song pattern formation in oscine songbirds are influenced by steroid hormones such as estrogens and androgens, and the control of vocal pattern generation is mediated via a network of interconnected vocal and respiratory nuclei. The main components of the respiratory part of the network are the expiratory and inspiratory premotor nuclei, known as retroambigualis (RAm) and the rostral ventral respiratory group (rVRG), respectively. These respiratory components play an integral role in song production either by providing the expiratory pulses of air required for each and every song syllable, or by controlling inspiration between syllables in the form of minibreaths, and between phrases for major replenishments of air. Here we analyze the distribution of androgen receptors (AR) and estrogen receptors (ER) in the midbrain and hindbrain of male and female zebra finches, and male canaries and green finches, using in situ hybridization with cRNA probes of the zebra finch AR and ER. ERmRNA was not expressed in any of the respiratory-vocal nuclei of the midbrain or hindbrain, but ARmRNA was expressed in the tracheosyringeal motor nucleus (nXIIts) and in RAm and rVRG. The size of the ARmRNA defined RAm and rVRG was similar in male and female zebra finches, but the size of ARmRNA defined nXIIts was slightly sexual dimorphic. Previously undescribed areas of ARmRNA expression outside the respiratory-vocal network in the brain stem were the nucleus semilunaris and layers 10-12 of the optic tectum. AR-mRNA expression in the respiratory-vocal nuclei of adult male songbirds, adult female zebra finches, and juvenile zebra finches suggests that the temporal pattern of learned and unlearned vocalizations is sensitive to androgen-dependent mechanisms mediated by RAm and rVRG.

Animals↗
PubMed1996

The ontogeny of the canary HVC revealed by the expression of androgen and oestrogen receptors.

The vocal control nucleus HVC (nucleus hyperstriatalis ventrale, pars caudale) of the canary (Serinus canaria) is a model in which to study the relationship between anatomical plasticity and vocal developmental learning. Much of the structural plasticity of the HVC is sensitive to the action of androgenic and oestrogenic gonadal hormones that affect the brain by binding to androgen receptors (AR) and oestrogen receptors (ER). Here we report developmental changes of AR and ER expression in the HVC using in situ hybridization with avian specific cRNA probes. AR and ER are first expressed in the HVC at post-hatching day 10 (P10) and P30, respectively and are, therefore, present in the HVC throughout the singing-learning period of the canary. Because AR occur only in the caudal neostriatum of the HVC we mapped the size of the HVC with this marker. The size and neurone number of the AR-defined HVC reaches adult values at P30 and differentiates, therefore, independently of the singing activity and probably independently of oestrogens. Continuing neurogenesis in the HVC requires neuronal death and replacement from P30 on.

Animals↗
PubMed1996

Developmental changes in the distribution of oestrogen receptor mRNA expressing cells in the forebrain of female, male and masculinized female zebra finches.

In female zebra finches, oestrogens induce a male-like development of forebrain song nuclei such as the hyperstriatalis ventrale, pars caudal (HVC) and robustus archistriatalis (RA) that are normally highly sexually dimorphic. The distribution of oestrogen receptor (ER) mRNA in the vocal control system of male, female and oestrogen-treated female zebra finches was assessed between the day of hatching and adulthood using in situ hybridizations with a zebra finch-specific ER probe. ER mRNA was first expressed in the caudal forebrain at posthatching (P) day P5 to P7. At this age, ER mRNA-expressing cells lined the lateral ventricle. This band of labelling extended into the medial portion of HVC from P15 onwards. ER mRNA was found in the shell of the RA from P20 onwards. ER were not expressed in other vocal control areas at any age. Thus oestrogens seem to induce ER-mediated differentiation of the vocal control system via action in the medial HVC, in the area along the lateral ventricle and in the shell of the RA. This differentiation does not involve oestrogen-induced upregulation of ER in vocal control areas. Since the distribution of ER mRNA in the caudal forebrain was similar in juvenile males and females, ER pattern does not explain the sex-specific differentiation of the song system.

Age Factors↗
PubMed1996

The development of a species difference in the local distribution of brain estrogen receptive cells.

Estrogen receptors (ER) are crucial for estrogen-dependent brain differentiation and for estrogen-dependent neural functions of vertebrates. ER are expressed in a area-specific pattern in the vertebrate brain. The mechanisms that lead to the area-specific expression of ER are unknown. Here we use a species difference in the ER distribution between quail and chick and isochronic and isotopic quail to chick transplants to investigate mechanisms underlying the development of area-specific expression of ER. The entire neural tube rostral to the 6th somite (n = 2) or rostral to the otic capsules (n = 4) were transplanted at the second day of incubation (E2). In immunocytochemical stainings with the ER antibody H222Sp gamma, there is a defined cluster of intensely immunostained cells in the ventrolateral preoptic area of adult quails (the QERN). At the time of grafting, the entire brain primordium lacks ER. The QERN expresses ER as early as E13. The homologous area of the chicken brain does not differentiate cells that contain ER at any stage after ER are first detectable in the chicken brain at E11. In contrast, quail-chick chimeras develop the QERN phenotype in the ventrolateral preoptic area similar to quails. This implies that some signal which commits cells to the QERN phenotype (ER expression) is present in the quail brain primordium rostral to the otic capsules by embryonic day 2, and that this signal is unaffected by subsequent exposure to the global chick environment.

Animals↗
PubMed1996

Identification, distribution, and developmental changes of a melatonin binding site in the song control system of the zebra finch.

In many avian species, singing is a circadian or seasonal behavior that appears to be widely dependent on gonadal steroid hormones. To explore the possibility of a further hormone-dependent vocal control mechanism driven by the action of melatonin, we examined the binding of iodinated melatonin (IMEL) in the vocal control network of adult and juvenile (22- and 40-day-old) zebra finches. IMEL binding areas of the zebra finch brain were localized and characterized by using quantitative in vitro autoradiography. In the vocal control system, dense IMEL binding sites were restricted to the nucleus hyperstriatalis ventrale, pars caudalis (HVC). The binding of IMEL to the HVC and to visual areas, e.g., the ectostriatum and the optic tectum, was saturable and showed a single class of high-affinity binding sites with binding affinities (Kds) in the range of 5-20 pM. Competition experiments with various indols and IMEL showed that the IMEL binding site in the zebra finch brain has properties similar to the high-affinity melatonin receptor described in the chicken, in the house sparrow, and in the mammalian brain and retina. Similar to the zebra finch HVC, the HVC of other songbirds, e.g., male canaries and male house sparrows, has the most intense IMEL binding of all areas of the vocal control network. The IMEL binding in the forebrain vocal control areas of the zebra finch, but not that in the visual processing areas, was sexually dimorphic in correlation with the sexually dimorphic neuroanatomy of the forebrain vocal control areas. In the HVC, there is a developmental increase in the maximal number of binding sites for IMEL and in the protein content, so that the adult phenotype of dense IMEL binding develops between day 40 and day 80. The distribution and developmental pattern of IMEL binding in the song system suggests that melatonin has a role in the motor control of singing. Melatonin binding sites in HVC could link HVC-based song control to circadian and circannual changes in the photoperiod independent of gonadal steroids.

Animals↗
PubMed1996

Testosterone-dependent increase of gap-junctions in HVC neurons of adult female canaries.

Singing of canaries is controlled by a chain of interconnected brain areas. One of these areas, the caudal nucleus of the ventral neostriatum (HVC), is sensitive to androgens and estrogens. In adult canaries, both male and female sing. Female song is structured differently from the male singing and characterized by a higher variability. Singing females were implanted with testosterone propionate (n = 5) or with empty silastic tubes (n = 5). Testosterone treated females developed a male-like song and had an increased number of neuronal soma-somatic gap junctions in the HVC compared with the untreated singing females. Electric coupling of HVC neurons could be important for the testosterone-dependent changes of the song pattern of canaries.

Animals↗
PubMed1996

Chronic granulomatous disease in adults.

BACKGROUND: Chronic granulomatous disease (CGD), an inherited disorder of granulocyte function caused by failure of intracellular superoxide production, normally presents in the first years of life with severe recurrent bacterial and fungal infections. METHODS: From the files of two children's hospitals we identified 11 CGD patients who were remarkable for an unusually late diagnosis, at 13-43 years of age. Their clinical and laboratory features were examined. FINDINGS: The first clinical manifestation occurred at a median age of 3.6 years but CGD was not diagnosed until a median age of 22 years. Pneumonias and abscesses caused by Staphylococcus aureus and Aspergillus species were the most frequent infections. Granulomas, often leading to chronic complications, occurred in 7 of the patients. With 1.1 severe infections in 100 patient months, the 11 patients had a lower frequency of severe infections than patients with classic CGD; however, such infections could be equally life-threatening. 8 of the patients had X-linked CGD with small but detectable quantities of cytochrome b558, normally absent in X-linked CGD; and 3 had autosomal-recessive CGD. 9 patients had residual production of reactive oxygen metabolites, a feature that could explain the low incidence of infections. INTERPRETATION: CGD in adults may be more common than previously assumed. In view of the possibility of timely treatment, infection prophylaxis, and genetic counselling for affected families, CGD should be excluded in any patient with unexplained infections or granulomas.

Abscess↗
PubMed1996

Efficacy of acellular pertussis vaccine in early childhood after household exposure.

OBJECTIVE: To evaluate the efficacy of a three-dose primary vaccination with a diphtheria-tetanus tricomponent acellular pertussis vaccine against "typical" pertussis, defined as a spasmodic cough of 21 days or longer with confirmation of Bordetella pertussis infection by culture or serology. DESIGN: Passive monitoring for suspected first household (index) cases of typical pertussis in six areas in Germany comprising 22,505 children vaccinated with study vaccine at 3, 4, and 5 months of age. Blinded, prospective follow-up of household contacts of index cases for incidence and progression of pertussis. SETTING: Six areas in Germany with a high incidence of pertussis. SUBJECTS: Four hundred fifty-three households with index cases comprising 360 evaluable contacts eligible for analysis of vaccine efficacy. MAIN OUTCOME MEASURE: Vaccine efficacy from attack rates of pertussis in household contacts classified by vaccination status. RESULTS: Of the 173 nonvaccinated household contacts, 96 developed typical pertussis, compared with seven of 112 contacts vaccinated with acellular pertussis vaccine. Vaccine efficacy was consequently calculated to be 88.7% (95% confidence interval, 76.6% to 94.6%). Protection did not wane until at least the time recommended for booster vaccination. None of the analyzed potential confounding factors--age, socioeconomic status, erythromycin treatment, household composition, center effect, and selection bias--influenced study results in favor of the vaccine. CONCLUSIONS: Under conditions of intense household exposure, primary vaccination with acellular vaccine protected against pertussis until at least the time recommended for booster vaccination. The vaccine can be expected to be equally or more effective in settings with lower infectious pressure.

Bordetella pertussis↗
PubMed1996

Clinical experience of a tricomponent acellular pertussis vaccine combined with diphtheria and tetanus toxoids for primary vaccination in 22,505 infants.

OBJECTIVES: To assess the safety and tolerability of 12 lots of SmithKline Beecham Biologicals' diphtheria-tetanus-tricomponent acellular pertussis vaccine (DTaP) in a large cohort of 22,000 vaccinees, with detailed analyses of reactivity, immunogenicity, and immune response to pertussis toxin in subsets. METHODS: In a prospective, double-blind, multicenter trial in Germany, 22,505 healthy infants received three vaccinations of DTaP at age 3, 4, and 5 months. Serious adverse events were followed for 1 month after each vaccination, and neurologic events for 1 year or longer. Serum IgG antibodies were assayed before vaccination and 1 month after vaccination. RESULTS: After 67,000 doses, 153 serious adverse events (0.23%) were reported, 8 considered possibly related, and 5 related to vaccination, including 1 hypotonic-hyporesponsive episode. Incidence rates of sudden infant death syndrome (7; 0.01%) or acute neurologic events (20; 0.030%) were no higher than expected and not considered to be related to vaccination. Redness and swelling of 20 mm or greater occurred after 44 (0.6%) and 40 (0.6%) of the 7270 doses, respectively, and high fever (> 39.5 degrees C) in 6 (0.08%) subjects within 48 hours of vaccination. In the immunogenicity analysis of 580 infants, 98% responded to pertussis toxin, 96% to filamentous hemagglutinin, and 98% to pertactin. In an additional 5712 infants, the response rate to pertussis toxin was 99%. CONCLUSIONS: In a large cohort of 22,505 infants vaccinated, SmithKline Beecham Biologicals' tricomponent DTaP vaccine was shown to be safe, well-tolerated, and immunogenic for all component antigens.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed1995

[Chronic granulomatosis: a rare differential diagnosis in liver granulomas in adulthood].

A now 43-year-old man was known since childhood to have mesenteric and subcutaneous lymphadenopathy. Histological examination of liver biopsies and excision of some lymph nodes when an adult showed epithelioid granulomas, in places with Langhans giant cells. Diagnostic splenectomy revealed no pathological findings. His present admission to hospital was for an infection with high fever. On auscultation moist rales were audible over the apex of the left lung. The chest radiography showed pneumonic infiltration. Blood culture grew Pseudomonas aeruginosa. Ultrasound demonstrated hypoechogenic homogeneous and smoothly circumscribed round foci in the liver hilus and around the coeliac trunk. The upper lobe pneumonia healed under antibiotic treatment. As chronic granulomatosis was suspected, the nitroblue tetrazolium and superoxide production tests were performed. They demonstrated that the capacity of the granulocytes to form oxygen radicals was markedly diminished. Chronic granulomatosis is an inherited disorder of granulocyte function linked to the X-chromosome. It must be included in the differential diagnosis of any unclear granulomatous disease even in adults.

Adult↗
PubMed1995

Reptilian sex steroid receptors: amplification, sequence and expression analysis.

Sex steroid hormones secreted by the gonads play a central role in the reproduction of all vertebrates. In addition to direct effects on gametogenesis, sex steroid hormones are important in sexual development, brain organization, and sexual behavior. The actions of sex steroid hormones are mediated primarily by ligand-dependent transcription factors, or receptors which bind to specific sequences of the DNA and alter the transcription rates of nearby genes. We have used the polymerase chain reaction to amplify cDNA fragments of the estrogen receptor, progesterone receptor and androgen receptor from the unisexual whiptail lizard, Cnemidophorus uniparens. The lizard steroid hormone receptors share a high degree of sequence homology to the steroid hormone receptors of other vertebrates. Ribonuclease protection assays demonstrate that both estrogen receptor mRNA and progesterone receptor mRNA are increased in the oviduct during vitellogenesis and after estrogen treatment. This report demonstrates the utility of the polymerase chain reaction to generate species specific probes for comparative molecular studies and provides the first report of cDNA sequences for reptilian steroid hormone receptors.

Amino Acid Sequence↗
PubMed1994

[Long-term treatment of patients with itraconazole for the prevention of Aspergillus infections in patients with chronic granulomatous disease (CGD)].

Chronic granulomatous disease (CGD) represents an innate immunodeficiency: the reduced production of oxygen radicals in phagocytosing cells results in decreased ability to kill pathogenic microorganisms. The patients concerned suffer from severe recurrent infections due to bacteria and fungi. Prophylactic administration of trimethoprim-sulfamethoxazole, as usual in CGD-patients, has markedly reduced the incidence of bacterial infections. Now as before, however, there is a high risk to become affected by invasive fungal infections, mainly due to Aspergillus spp. which often are lethal. Therefore, a well-compatible antimycotic long-term prophylaxis effective against Aspergillus would be attractive. In the present study the compatibility of the oral triazole itraconazole was tested in 8 CGD-patients with high risk of Aspergillus infections. Itraconazole was administered in capsules with a dosage of 5.1 mg/kg body weight per day on an average for a mean range of 23 months. Periodically liver enzymes, renal retention and electrolytes were assessed as well as itraconazole serum levels. Aspergillus serology tests included complement fixation tests, IgG-ELISA, precipitation tests, IgE determination and Aspergillus-RAST. During the prophylactic treatment in all of the 8 patients no gastrointestinal side effects or hypersensitivity reactions were observed. Renal retention and serum electrolytes as well as liver enzyme values were in normal ranges with all patients. Itraconazole serum levels showed a marked intra- and interindividual variability. However, 82% of the peak levels were in ranges regarded as therapeutically effective for itraconazole. Under prophylaxis a clear decrease of Aspergillus IgG-ELISA values was observed in 5 of 7 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[HIV infection and AIDS in urology].

Up to December 1993, a total of 10858 AIDS cases were reported to the central AIDS registry at the Federal Health Office. Human immunodeficiency virus is acquired through needle sharing (i.v. drug users), contaminated blood transfusions, intercourse with infected persons and transplacentally by fetuses. In Germany, about seven people a day are estimated to acquire the HIV infection. Half the patients will develop systemic manifestations of AIDS within 12-13 years. Only a small percentage of these patients suffer from urological manifestations, e.g. urinary tract infection, prostatism or HIV-associated nephropathy. Nevertheless, knowledge of genitourinary pathology caused by HIV makes early diagnosis of AIDS possible.

AIDS-Related Opportunistic Infections↗
PubMed1993

Improvement of superoxide production in monocytes from patients with chronic granulomatous disease by recombinant cytokines.

Cytokines have been shown to modulate the respiratory burst of polymorphonuclear leukocytes and monocytes from normal controls. We have examined whether monocytes from children with chronic granulomatous disease (CGD) can be primed by cytokines other than interferon-gamma (IFN gamma), which has been demonstrated to improve the production of reactive oxygen species in vivo and in vitro. Monocytes isolated from peripheral blood were cultured without and with IFN gamma (500 U/mL), tumor necrosis factor-alpha (500 U/mL), interleukin-1 beta (IL-1 beta) (100 U/mL), and IL-3 (100 U/mL). After 3 days of culture, the phorbolmyristate acetate (2 ng/mL) and the formyl-methionyl-leucyl-phenylalanine (0.1 mumol/L)-stimulated superoxide-production was determined in a microtiter system. In nearly all of the 14 patients examined (5 autosomal, 5 X-chromosomal, and 4 of unknown inheritance), an improvement of superoxide production could be demonstrated. The most impressive effect with the cytokines newly tested was seen with monocytes from autosomal CGD patients treated with IL-3 and stimulated by phorbolmyristate acetate. In single patients cultivation of monocytes with IL-6 and granulocyte-macrophage colony-stimulating factor resulted in only slight improvement of superoxide production. Our findings indicate that cytokines other than IFN gamma can positively modulate the defective respiratory burst in CGD and that each patient reacts with an individual pattern to different cytokines.

Cells, Cultured↗
PubMed1993

Estrogen receptors in the avian brain: survey reveals general distribution and forebrain areas unique to songbirds.

Estrogens play an important role in the control and differentiation of species-typical behavior and in endocrine homeostasis of birds, but the distribution and evolution of cells that contain estrogen receptors in the avian brain are poorly understood. This study therefore surveys 26 species in the avian orders Anseriformes (1 species), Galliformes (2), Columbiformes (3), Psittaciformes (1), Apodiformes (2), and Passeriformes (3 suboscines, 14 oscines). Indirect immunocytochemistry with the estrogen receptor (ER) antibody H222Spy revealed a general pattern of ER-antibody-immunoreactive cells (ER-IRC) in all 26 species, with ER-IRC in consistent, well-defined locations in the limbic forebrain, the midbrain striatum, the hippocampus, the hindbrain, and especially in the preoptic area and the tuberal hypothalamus. For some species, the microdistribution of ER-IRC in some of these general areas differed, such as in the hippocampus and the anterior hypothalamus of suboscine species and in the preoptic area of the Japanese quail. Brains of oscine songbirds of both sexes, unlike brains of nonsongbirds, had ER-IRC in three specific structures of the nonlimbic forebrain: in the area surrounding the nucleus robustus archistriatalis; in the rostral forebrain; and, for all individuals, in the caudale neostriatum, including the nucleus hyperstriatalis ventrale, pars caudale (HVc). Among songbird families or subfamilies, adult males of the Estrildinae had much lower numbers of ER-IRC in HVc than did adult males of the Fringillidae, Paridae, Sturnidae, and Ploceinae. Differences occurred, too, among closely related species: the songbird canary (Serinus canaria) had an ER-IRC area in the rostral forebrain that was lacking in all other songbird species, including other cardueline finches. The cells with ER that are found only in the songbird forebrain but not in reptiles, nonpasserine birds, and nonoscine passerine birds very likely coevolved with steroid-dependent differentiation of vocal control areas. The songbird-specific expression of ER in the forebrain could be an example in which taxon-specific behavior is due to taxon specific neurochemical properties of the brain.

Age Factors↗
PubMed1993

Reduced secretion of interleukin-1 and tumor necrosis factor-alpha by neonatal monocytes.

Monocytes were isolated from peripheral blood of preterm and term newborn infants and adult controls, and their capacity to secrete the inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) was investigated. Lipopolysaccharide (LPS)-stimulated neonatal monocytes secreted significantly less IL-1 (median: 1.1 U/ml) than monocytes from adult controls (median: 7.3 U/ml). In addition TNF-alpha production by LPS-stimulated neonatal monocytes (median: 610 pg/ml) was significantly lower when compared with controls (median: 2230 pg/ml). Our data provide evidence that neonatal monocytes have a profoundly impaired cytokine secretion.

Adult↗