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Biomedical subjects

K Bergmann

Publications and source records attributed to K Bergmann.

At least 19 recordsLinked to original sources
PubMed2001

Epigenetic targeting in the mouse zygote marks DNA for later methylation: a mechanism for maternal effects in development.

The transgenic sequences in the mouse line TKZ751 are demethylated on a DBA/2 inbred strain background but become highly methylated at postimplantation stages in offspring of a cross with a BALB/c female. In the reciprocal cross the transgene remains demethylated suggesting that imprinted BALB/c methylation modifiers or egg cytoplasmic factors are responsible for this striking maternal effect on de novo methylation. Reciprocal pronuclear transplantation experiments were carried out to distinguish between these mechanisms. The results indicate that a maternally-derived oocyte cytoplasmic factor from BALB/c marks the TKZ751 sequences at fertilization; this mark and postzygotic BALB/c modifiers are both required for de novo methylation of the target sequences at postimplantation stages. Using genetic linkage analyses we mapped the maternal effect to a locus on chromosome 17. Moreover, seven postzygotic modifier loci were identified that increase the postimplantation level of methylation. Analysis of interactions between the maternal and the postzygotic loci shows that both are needed for de novo methylation in the offspring. The combined experiments thus reveal a novel epigenetic marking process at fertilization which targets DNA for later methylation in the foetus. The most significant consequence is that the genotype of the mother can influence the epigenotype of the offspring by this marking process. A number of parental and imprinting effects may be explained by this epigenetic marking.

Alleles↗
PubMed2000

Molecular biology and clinical manifestation of hereditary factor VII deficiency.

Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder. Mutations and polymorphisms of the FVII gene were characterized in more than 40 unrelated patients with FVII deficiency. Among the 29 different mutations, the most frequent were Ala294 Val, Ala294Val;404delC, IVS7+7, and Val281 Phe. Four novel mutations (IVS2+1G>C, Arg247 Cys, Glu265 Lys, Asp343 His) were detected. The relationships between genotypes of mutations and polymorphisms of the FVII gene, FVII deficiency, and clinical phenotype were investigated. Homozygosity of the Phe4 Leu, IVS4+1G>A, Cys135 Arg, Ala244 Val, and Ala294 Val;404delC and the double heterozygosity of Tyr68 Cys / IVS3-1G>A, Val252 Met / IVS2+5G>T, Val281 Phe / Cys135 Arg, Ala294 Val / Val281 Phe, Ala294 Val;404delC / Val281Phe, Ala294 Val;404delC / Arg152 stop, Ala294Val;404delC / Gln(-35) stop, Ala294 Val / Val252 Met, Ala294 Val / Gly156 Asp, and Thr359 Met / Asp242 His were related to clinical symptoms. Double heterozygotes for Arg247 Cys / IVS2+1G>C, Ala206 Thr / Pro303 Arg, Leu(-20) Pro / Val252 Met as well as IVS7+7 /Ala294 Val, IVS7+7 /Ala206 Thr, and IVS7+7 / Met298 Ile were asymptomatic. The clinical symptomatology is rather poor in correlation with the FVII activity. Concerning the clinical phanotype, a correlation seems to exist between specific mutations and clinical symptoms.

Factor VII↗
PubMed2000

Respimat (a new soft mist inhaler) delivering fenoterol plus ipratropium bromide provides equivalent bronchodilation at half the cumulative dose compared with a conventional metered dose inhaler in asthmatic patients.

BACKGROUND: Respimat, a possible alternative to the conventional metered dose inhaler (MDI), is a novel, reusable, propellant-free, multidose soft mist inhaler. Respimat slowly releases a metered dose of active substance as a soft mist with a high proportion of the dose in the fine particle fraction, leading to improved lung deposition following inhalation when compared with the conventional MDI. OBJECTIVES AND METHODS: The equipotent bronchodilating efficacy and safety of a combination of fenoterol hydrobromide and ipratropium bromide (F/I) in cumulative doses delivered by either Respimat or pressurised MDI was assessed in a randomised, controlled, double-blind (within device) 4-way crossover study. Forty-three patients with stable asthma (mean FEV(1) 62% predicted) responsive to F/I inhaled cumulatively 16 puffs on each of 4 test days (1 + 1 + 2 + 4 + 8 puffs at 50-min intervals) via Respimat delivering 50/20, 25/20 or 25/10 microg F/I per puff or via MDI delivering 50/20 microg F/I per puff. RESULTS: Cumulative doses of 400/160 and 400/320 microg F/I via Respimat produced bronchodilation (evaluated by average increase in FEV(1) 45-245 min after first inhalation) equivalent to that achieved with a cumulative 800/320 microg F/I via MDI (mean increase in FEV(1) above baseline 0.76, 0.73 and 0.71 litres, respectively). The tolerability of the F/I combination via Respimat was also comparable to that of twice the dose delivered via MDI. CONCLUSION: Therefore, a fenoterol hydrobromide/ipratropium bromide combination delivered by Respimat is as safe and effective as the MDI at half the cumulative dose, on acute administration to patients with asthma.

Administration, Inhalation↗
PubMed1998

The genomes of three of four novel HPV types, defined by differences of their L1 genes, show high conservation of the E7 gene and the URR.

The DNA genomes of four new human papillomaviruses, HPV 75, HPV 76, HPV 77, and HPV 80, have been cloned, sequenced, and characterized. HPV 75, HPV 76 (both HPV 49-related), and HPV 77 (HPV 29-related) were isolated from benign cutaneous warts and HPV 80 (HPV 15-related) from histologically normal skin. HPV 77 has also been demonstrated in dysplastic warts and squamous cell carcinomas of the skin. The sequence data presented in this study led to a proposed modification of the definition of a new HPV type. The high degree of DNA sequence similarity between the E7 ORF of HPV 77 and HPV 29 (97.7%), as opposed to the E6 (82.8%) and L1 (85.3%) ORFs, might suggest conservation of a specific function or a possible recombinational event. Only the E6 and L1 ORFs of HPV 75 and HPV 76 have a similarity lower than 90%, whereas the DNA sequences of their upstream regulatory regions (URRs) share a similarity of 93%. The E7, E1, and E4 ORFs, as well as the URR of HPV 15 and HPV 80, share sequence similarities higher than 90%. Such a divergence in the similarity between different segments of the virus genomes of closely related HPV types has not been noted to date. A detailed comparative sequence analysis was performed. HPV 75, HPV 76, and HPV 80 revealed features characteristic of truly cutaneous HPV types, whereas HPV 77 shared several characteristics with the mucosal HPV types, some of which may have functional consequences.

Amino Acid Sequence↗
PubMed1998

[Disparities in hospital mortality after proximal femoral fractures in East Germany 1989].

The revised and pseudonymized data set of the hospital discharge diagnoses of East Germany (German Democratic Republic, GDR) for 1989 was analyzed regarding the in-hospital case fatality of closed hip fractures (ICD-9 820.0, 820.2, 820.8). The case fatality of 20.2% during an average hospital stay of 60 days including between-ward and between-hospital transfers is high when compared to international data and data for West Germany. Apart from the expected influence of age, fatality was reduced for cervical (intracapsular) fractures, female sex, and for a location of the treating hospital within East Berlin. This reduction of the case fatality within East Berlin by nearly two thirds after adjustment for age, sex, and type of fracture compared to other regions is most likely explained by better medical treatment facitilities within East Berlin, the former capital of the GDR. The regional disparities that were observed during our model analysis give a hint towards the influence that medical care can have on the fatality associated with this on a population level relevant disease.

Adult↗
PubMed1998

Recovery of Cryptosporidium oocysts from small and large volume water samples using a compressed foam filter system.

A novel filter system comprising open cell reticulated foam rings compressed between retaining plates and fitted into a filtration housing was evaluated for the recovery of oocysts of Cryptosporidium from water. Mean recoveries of 90.2% from seeded small and large volume (100-2000 l) tap water samples, and 88.8% from 10-20 l river water samples, were achieved. Following a simple potassium citrate flotation concentrate clean-up procedure, mean recoveries were 56.7% for the tap water samples and 60.9% for river water samples. This represents a marked improvement in capture and recovery of Cryptosporidium oocysts from water compared with conventional polypropylene wound cartridge filters and membrane filters.

Animals↗
PubMed1997

Chlorodibromomethane metabolism to bromide and carbon monoxide in rats.

The chlorodibromomethane (CDBM) metabolites bromide and CO were analysed as bromide level in plasma and carboxyhaemoglobin (COHb) level in blood of rats, respectively. The mean basic levels of bromide in plasma of rats receiving vehicle were 0.075 +/- 0.036 mmol/l (n = 27). After administration of CDBM at 0.4, 0.8, 1.6, and 3.1 mmol/kg p.o., the mean bromide levels rose to maximal values that were higher by a factor 27, 48, 69, and 135, respectively. Bromide elimination was slow and the plasma level was significantly increased following repeated administration in comparison to a single administration of CDBM. The CDBM concentrations in blood and in fat tissue 6 h after the last of 7 administrations of 0.8 mmol CDBM/ kg p.o., once a day for 7 consecutive days, were significantly lower than 6 h after a single gavage of this CDBM dose. The mean normal level of 0.45 +/- 0.32% COHb in rats (n = 30) was significantly increased following oral CDBM uptake. Initially higher COHb levels were measured after 7 consecutive applications of 0.8 mmol/kg CDBM. After a single administration of CDBM the level of glutathione disulphide in the liver was significantly increased; this effect was reversible. The oxidative CDBM metabolism was influenced by the glutathione (GSH) concentration in the liver. The rate of COHb and bromide formation was decreased after GSH depletion due to pretreatment of rats with buthionine sulphoximine (BSO) and increased following enhancement of the GSH concentration due to pretreatment of the animals with butylated hydroxyanisole (BHA). CDBM is a substrate for cytochrome P-450 2E1 (CYP2E1), as demonstrated by the inhibition of bromide and COHb formation due to simultaneous administration of CDBM and the CYP2E1 inhibitor diethyldithiocarbamate (DDTC); also by the initially higher levels of bromide in plasma and COHb in blood after gavage of CDBM pretreated with isoniazid (INH), an inducer of CYP2E1. The increase of bromide formation after CDBM administration in phenobarbital (PB)-pretreated rats indicated that cytochrome P-450 2B1 and 2B2 (CYP2B1 and CYP2B2) play a role as catalysts of the CDBM biotransformation. It is shown that m-xylene pretreatment, which activates CYP2E1 as well as CYP2Bs, leads to a higher bromide level after CDBM administration than the INH or PB pretreatment. In liver microsomes of rats treated with CDBM (0.8 mmol/kg p.o., seven daily applications), the p-nitrophenol hydroxylase (p-NPH) activity, a market of CYP2E1, was increased. It is concluded that CDBM may be an inducer of CYP2E1. These results combined with literature data demonstrate that the oxidation of CDBM was catalysed mainly by CYP2E1 and CYP2Bs and that there may be a risk of bromide accumulation following repeated uptake of the trihalomethane.

Animals↗
PubMed1997

Indoor allergen exposure is a risk factor for sensitization during the first three years of life.

BACKGROUND: The purpose of the study was to investigate the influence of environmental allergen exposure on allergic sensitization in infancy and early childhood. METHODS: A cohort of 1314 newborns was recruited and followed up prospectively at the ages 12, 24, and 36 months. The levels of major mite (Der p 1 and Der f 1) and cat (Fel d 1) allergens were determined from domestic carpet dust samples by sandwich ELISA. Specific serum IgE antibodies to mite and cat allergens were determined by CAP fluoroimmunoassay (Pharmacia). Logistic regression was used to assess the effects of allergen exposure, age, family history, and cord blood IgE simultaneously on the risk of sensitization. RESULTS: Children, who had been found to be sensitized at least once during the first 3 years of life, were found to be exposed to significantly higher house dust mite (median, 868 ng/gm vs 210 ng/mg; p = 0.001) and cat (median, 150 ng/gm vs 64 ng/gm; p = 0.011) allergen concentrations in domestic carpet dust compared with the group without sensitization. In homes with low (< or = 25th percentile) dust concentrations, the risk of sensitization to mite (1.6%), and cat (2.0%) is low, compared with 6.5% for mite and 6.3% for cat if the domestic exposure is above the 75th percentile. The dose-response relationships between allergen levels and sensitization indicate that the increase in sensitization risk at low allergen levels is more pronounced in cat allergy (p = 0.002) than in mite allergy (p = 0.026). In the group with a positive family history, lower mite and cat allergen concentrations are needed to achieve specific sensitization compared with the group with a negative family history. CONCLUSION: Our data indicate that avoidance measures in the domestic environment aimed at the primary prevention of allergen-driven sensitization should be introduced at the earliest possible stage, if possible during infancy.

Air Pollution, Indoor↗
PubMed1997

Case report: pathomorphology of an experimental disseminated Aspergillus fumigatus infection in rabbits.

In following a formerly successful protocol designed to produce antibodies to A. fumigatus (Fres) we observed a disseminated, lethal fungal infection in healthy, specific pathogen-free (SPF) rabbits. The pathomorphological findings included multiple miliary to avenaceous whitish nodules in the livers and kidneys, mycotic mesencephalitis, nephritis, hepatitis, myocarditis, hemorrhagic enteritis, and splenitis. The hyphae were surrounded by necrosis, which also occurred in the liver without the hyphae. Comparative gas chromatographic and metabolic investigations on this strain and some environmental A. fumigatus strains showed significant differences. The findings are discussed with particular reference to the pathogenicity of A. fumigatus.

Animals↗
PubMed1997

[Whole body distribution of Tc-99m-sestamibi after pharmacological stress with arbutamine and dipyridamole compared with resting conditions].

AIM: Arbutamine is a new catecholamine that has been developed as a pharmacologic stress agent for the diagnosis of coronary artery disease. Optionally, it can be used in myocardial scintigraphy. The pharmacologic effect compared to dipyridamole was assessed looking at the whole body distribution of Tc-99m-Sestamibi. METHODS: 9 patients were investigated after injection of Tc-99m-Sestamibi during rest, after infusion of arbutamine, and after vasodilatation with dipyridamole. RESULTS: Infusion of arbutamine results in a measurable diminished radiotracer deposition in the lower limb as compared to dipyridamole. The amount of myocardial activity of Tc-99m-sestamibi, however, is also reduced as shown by the percentage of myocardial activity compared to the whole body distribution (2.5% +/- 0.4% for arbutamine vs. 2.8% = 0.5% for dipyridamole) in addition, the heart/lung ratio is lower after application of arbutamine (12.1% +/- 0.5% vs. 2.4% +/- 0.4%). CONCLUSION: After infusion of arbutamine the percentage of myocardial activity as well as the contrast of the myocardium to the surrounding lungs is decreased as compared to dipyridamole. Further studies should reveal whether this difference is relevant in diagnosing coronary artery disease.

Adrenergic beta-Agonists↗
PubMed1996

Speciation of organolead compounds in water samples by GC-AAS after in situ butylation with tetrabutylammonium tetrabutylborate.

A simple and reliable analytical method for the determination of organolead compounds in water samples has been developed by means of a gas chromatographic-atomic absorption system (GC-AAS). The derivatization of the organolead cations, necessary before their determination, was directly achieved in the water samples by the reagent tetrabutylammonium tetrabutylborate. Hexane/pentane was used to extract the butylated tetraorganolead compounds. The organic layer was dried and purified with sodium sulfate, concentrated by evaporation and injected into a GC-AAS system. The effects of various parameters on the derivatization and extraction procedures were studied and discussed.

Journal Article↗
PubMed1995

[Doppler ultrasound studies of long-term follow-up of children with hemolytic-uremic syndrome].

AIM: In the present study, we compared the diagnostic value of Doppler sonography with "B-Imaging" in the acute and chronical period of the HUS in children. METHOD: For this, we analysed the Doppler sonographic measurement (Acuson-128) from 3 patients in the acute stage of the disease and 14 patients after approximately 5 years. All patients examined in the chronic stage of the disease had been treated by peritoneal dialysis in the acute stage. As a control, the Doppler sonographic analysis of the A. renalis was performed in 25 healthy children. RESULTS: During the acute phase of the HUS, we found a significant increase in both the resistive index (RI) and the pulsatility index (PI). In addition, the diastolic current in the A. renalis was decreased or the blood flow was reversed. The kidney volume as well as the echo was increased in all cases. A recovery of the kidney observed as beginning diuresis coincided with a return to normal parameters in the Doppler sonographic measurement. In patients examined after 5 years, both the RI and the PI value was significantly (p < 0.01) different from the control group. These parameters correlate with the effective renal plasma flow, but not with the glomerular filtration rate. CONCLUSION: We conclude that in the acute stage of the HUS either "B-Imaging" or duplex sonography yield pathological parameter values. For the observation of the renal symptoms during the chronic phase of the disease, duplex sonography is clearly superior.

Acute Disease↗