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Biomedical subjects

V Wahn

Publications and source records attributed to V Wahn.

At least 37 records · Page 2Linked to original sources
PubMed1998

Pilot study of zidovudine-lamivudine combination therapy in vertically HIV-infected antiretroviral-naive children.

OBJECTIVE: To examine tolerance and efficacy of a zidovudine plus lamivudine combination in HIV-infected children without previous exposure to antiretroviral drugs. METHODS: Thirteen vertically infected children (aged 4 months to 10 years) were treated with zidovudine (approximately 100 mg/m2 three times daily) and lamivudine (4 mg/kg twice daily). CD4 T-cell count, plasma HIV RNA concentration, complete blood count and blood chemistry profile were monitored before treatment and at months 1, 3 and 6. RESULTS: In general, treatment was well tolerated. One child developed slight neutropenia in the presence of antineutrophil antibodies. CD4 cell count increased from 851+/-621 x 10(6)/l at baseline to 1073+/-945 x 10(6)/l at month 3 (P < 0.05) and to 1133+/-728 x 10(6)/l at month 6 (P = 0.01). CD4+ cell count increased in 10 patients after 3 months and in 11 patients treated for 6 months. One child showed a continuous decrease of CD4 cells despite treatment. Before treatment the plasma HIV RNA concentration was elevated in nine children (> 4.0 log10 copies/ml) and decreased in all of them: by month 1, the mean reduction was -1.16 log10 copies/ml; by month 3, -1.38 log10 copies/ml; and by month 6, -1.53 log10 copies/ml compared with baseline. However, one child showed steadily increasing viral load from 2.7 log10 copies/ml to a maximum of 4.52 log10 copies/ml, surprisingly in association with increasing numbers of CD4 cells. This child was switched to a new combination regimen after 6 months of treatment. Plasma HIV RNA levels below limit of detection were reached in six patients: after 1 month of treatment in one patient, after 3 months in five patients, and after 6 months in six patients. There was a mean reduction of viral load from 4.56 log10+/-4.63 log10 copies/ml (n = 13) to 3.8 log10+/-3.9 log10 copies/ml (P < 0.05; n = 9) after 1 month, to 3.67 log10+/-3.88 log10 copies/ml (P < 0.01; n = 13) after 3 months, and to 3.64 log10+/-3.95 log10 copies/ml after 6 months of treatment (P < 0.001; n = 13). CONCLUSIONS: This pilot study demonstrates the feasibility of zidovudine-lamivudine combination in children not previously exposed to antiretroviral drugs. This promising combination should therefore be evaluated in larger trials.

Anti-HIV Agents↗
PubMed1998

Reverse mutations--spontaneous amelioration or cure of inherited disorders?

Some recent publications indicate that inherited disorders can ameliorate or possibly disappear if mutations responsible for the disease revert to normal. This review tries to summarize our current knowledge about reverse mutations as this information may be of special interest for attempts at somatic gene therapy.

Child↗
PubMed1998

Cord blood-IgE as risk factor and predictor for atopic diseases.

BACKGROUND: Cord blood-IgE as risk factor or predictor for atopic diseases in infants has been discussed in a large number of papers with contradictory results. Our aim was to evaluate cord blood-IgE as risk factor and predictor for atopic dermatitis, recurrent wheezing and sensitization with emphasis on a clear-cut distinction between risk factor and predictor. METHODS: A cohort of 1314 newborns was recruited in six German obstetric departments and followed-up for 5 years. Four hundred and ninety-nine infants (38%) were considered to be at high risk with at least two atopic family members and/or a cord blood-IgE value above the threshold of 0.9 kU/L. At follow-up visits, parents filled in a questionnaire, the infants were clinically examined, and blood samples were taken. RESULTS: With regard to early onset atopic dermatitis up to 12 months we found that the odds ratios at the cord blood-IgE cut-off points of 0.70 kU/L and 1.25 kU/L with values of 0.53 and 0.32, respectively, were smaller than one (i.e. protective factors) and highly statistically significant. No significant association was found between elevated cord blood-IgE and recurrent wheezing. There was a strong positive association between elevated cord blood-IgE levels and sensitization at 12 months, but even in this case the predictive performance was rather poor: a maximum positive predictive value of 42% was attained with a cut-off point of 3.0 kU/L, but the sensitivity was only 10%. CONCLUSION: We conclude that even when elevated cord blood-IgE levels are identified as a strong risk factor for sensitization, their poor predictive performance may make them useless as a basis for preventive measures.

Child, Preschool↗
PubMed1998

Atopic dermatitis in early infancy predicts allergic airway disease at 5 years.

BACKGROUND: Screening tests for atopy risk in newborns have a low predictive value. If early atopic symptoms and signs could be used as predictors for the next expected atopic disorder then secondary prevention could be employed. The aim of this study was to evaluate the capacity of early atopic dermatitis to predict aeroallergen sensitization and the manifestation of respiratory atopic disorders at 5 years of age. METHODS: 1314 children of a German prospective birth cohort study MAS-90 were followed from birth up to 5 years of age. Atopic dermatitis, asthma and rhinoconjunctivitis were diagnosed from symptoms and signs at physical examinations and by interviews of the parents. Blood was drawn at 1, 2, 3, and 5 years of age. Aeroallergen sensitization was diagnosed by a specific IgE value of at least 0.35 kU/L (CAP class > or = 1) against any of five respiratory allergens (mite, cat, dog, birch, grass). RESULTS: Atopic dermatitis in the first 3 months was a risk factor for aeroallergen sensitization at 5 years. The risk increased with a positive family history for atopic diseases. Seventy-seven per cent of children with two atopic parents and early atopic dermatitis were sensitized against aeroallergens at 5 years, i.e. could have been predicted in early infancy without any laboratory tests. Although these risk factors were also significantly associated with the manifestation of allergic airway disease, the positive predictive value for this outcome at age 5 years was not yet as high, i.e. 50%. CONCLUSION: Infants with very early signs of atopic dermatitis and a positive family history are candidates for early intervention measures against respiratory allergies.

Allergens↗
PubMed1998

CD28 expression in pediatric human immunodeficiency virus infection.

Increased apoptosis of lymphocytes represents a key event of immune destruction in HIV infection. In this study it was investigated at which stage of the disease and in which T lymphocyte subpopulation (CD4+ or CD8+) protection against apoptosis may be lost as measured by decreased CD28 expression. In 26 HIV-infected and 20 healthy children, as well as 10 infants exposed to HIV, expression of CD28 and the apoptosis-related marker CD95 was studied by fluorescence-activated cell sorting analysis. According to established Centers for Disease Control and Prevention definitions, children were divided into three immunologic categories. In the CD8 population, patients in category 1 already showed a markedly decreased mean CD28 (36.2%+/-16.1 SD) and increased CD95 expression (48.8+/-24.1%), compared with the age-matched control group (67.7+/-14.4%, 15.8+/-8.9%). In the CD4 population, mean CD28 and CD95 expression was not altered in category 1 patients. Of the exposed children, the child with the lowest CD28 expression on CD8 cells was determined later to be infected with HIV. Significant immunophenotypical alterations are observed in early stage pediatric HIV infection, which may indicate an early loss of protection against apoptosis in the CD8+ T cell population.

Adolescent↗
PubMed1997

Evidence for linkage of chromosome 12q15-q24.1 markers to high total serum IgE concentrations in children of the German Multicenter Allergy Study.

Linkage of asthma and high total serum IgE levels to chromosome 12q15-q24.1 has been recently described. To evaluate this region further in regard to total IgE responsiveness, we genotyped 52 unrelated German children with persistently "high" total serum IgE (selected from a noninterventional prospective multicenter cohort study) and their parents. We carefully defined a most extreme IgE phenotype and analyzed it as a dichotomous trait. We tested for linkage between high total IgE concentrations and nine polymorphic microsatellite markers on chromosome 12q15-q24.1 using the transmission/disequilibrium test. Evidence for linkage and allelic association for high total IgE was observed for four markers in this region. This study demonstrates the value of using extreme phenotypes in genetic analysis of a complex quantitative trait.

Child, Preschool↗
PubMed1997

The fat emulsion agglutination test: a reliable and cost effective alternative to the latex agglutination test for rapid bedside CRP measurement.

We compared two tests for bedside C reactive protein (CRP) measurement: the latex agglutination test (LAT) and the fat agglutination test (FAT). FAT is based on the property of CRP to agglutinate fat emulsions in the presence of CaCl2. The sensitivity, specificity and accuracy of FAT and LAT to detect a CRP > 10 mg/l, determined with radial immunodiffusion (n = 500 pediatric patients, CRP range 0- > 80 mg/l), were 91%, 82% and 90% respectively for FAT and 82%, 95% and 85% for LAT. FAT reagent could be stabilized with NaN3 (0.02%) for at least one year, when stored at 4 degrees C (n = 49). NaN3 (0.02%) had no effect on agglutination of FAT (n = 40). In conclusion, in pediatric patients, FAT is a reliable and cost effective alternative to LAT, if serum samples are used.

Agglutination Tests↗
PubMed1997

Nitric oxide mediates intracytoplasmic and intranuclear zinc release.

We previously described that NO. leads to destruction of ZnS clusters and release of Zn2+ from various proteins including zinc finger transcription factors. To assess the relevance in living cells, we investigated, whether exogenous NO. leads to an increase of cytoplasmic and nuclear free Zn2+. L929 cells, mouse splenocytes, or rat aorta endothelial cells were labeled with Zinquin-E, a Zn2+-specific fluorophore, and were treated with two different spontaneous NO donors, S-nitrosocysteine or DETA/NO. Both NO donors strongly increased the Zn2+-dependent fluorescence in the cellular cytosol and also in nuclei as compared to controls. NO-dependent Zn2+ release in splenocytes was quantitated by flow cytometry. These results show for the first time, that nitrosative stress mediates intracellular and intranuclear Zn2+ release which may be relevant in altering gene expression patterns.

Animals↗
PubMed1997

Anti-ganglioside monoclonal antibody AA4 selectively inhibits IgE-induced signal transduction pathways in rat basophilic leukemia cells.

In rat basophilic leukemia 2H3 (RBL-2H3) cells, mAb AA4 binds to two derivatives of ganglioside GD1b that associate with the Src family kinase p53/56lyn and a serine kinase. Pre-incubation of cells with mAb AA4 blocks immunoglobulin E (IgE) mediated histamine release. In the present study we investigated the effect of incubation with mAb AA4 on signal transduction events. In addition to stimulation of the high affinity IgE receptor (Fc epsilonRI), cells were also activated by the calcium ionophore A23187 and the acetylcholine agonist carbachol in RBL-2H3 cells transfected with the G protein-coupled m3 muscarinic receptor. Incubation of cells with mAb AA4 in a dose-dependent manner inhibited the following Fc epsilonRI-induced signal transduction events: the increase of intracellular free calcium, phosphoinositol breakdown, tyrosine phosphorylation of proteins including the beta- of Fc epsilonRI and secretion. However, there was no inhibition of degranulation or of these biochemical events when cells were stimulated with calcium ionophore or activated via a G protein-coupled pathway. Our results demonstrate that mAb AA4 selectively blocks Fc epsilonRI-induced cell activation at a very early step upstream of receptor tyrosine phosphorylation. As mAb AA4 has previously been found to bind to gangliosides associated with Fc epsilonRI, inhibition of very early biochemical events may be due to interaction of mAb AA4 with the Fc epsilonRI induced signal transduction cascade at the receptor level.

Animals↗
PubMed1997

Expression of mRNA for the proto-oncogene c-fos in rat basophilic leukaemia cells.

Recently, the expression of the mRNA for the proto-oncogene c-fos following activation of the high-affinity receptor for immunoglobulin E in rodent mast cells has been reported. In the present study we investigated different biochemical events that may play a role in signal transduction pathways culminating in the expression of c-fos mRNA in rat basophilic leukaemia cells. Similar to IgE-mediated cell degranulation we demonstrated inhibition of the c-fos signal in the absence of calcium and after preincubation of cells with the protein tyrosine kinase inhibitor genistein. Activation of RBL-2H3 cells by short term PMA treatment failed to induce cell degranulation or expression of mRNA for c-fos. Depletion of protein kinase C by PMA pre-treatment resulted in substantial inhibition of the c-fos signal. In contrast to IgE-mediated cell degranulation, expression of mRNA for c-fos was not dependent on continued receptor aggregation. In addition, we demonstrate that c-fos mRNA expression is not restricted to Fc epsilon RI activation but can be induced by a variety of IgE independent mechanisms including calcium influx by ionophore A 23187 and stimulation of G proteins.

3T3 Cells↗
PubMed1997

Antimicrobial functions of human monocytes depend on concentration of glutamine in vitro.

We investigated the impact of different concentrations of glycyl glutamine on antimicrobial functions of human monocytes in vitro. Generation of suproxide anion, phagocytosis and killing capacity were measured as an expression of antimicrobial activity after an incubation period of 38 h at glycyl glutamine concentrations of 0.0, 0.4, and 2.0 mmol/l respectively. For each of the tests, significantly higher results were obtained with concentrations of glycyl glutamine of 0.4 mmol/l as compared to 0.0 mmol/l (p < 0.01). Further increases of superoxide anion production (p < 0.05) and killing capacity (p = 0.053) were observed when glycyl glutamine concentration in the culture medium was raised to 2.0 mmol/l. Variation of glycyl glutamine concentrations in vitro significantly affects antimicrobial functions of human monocytes.

Anions↗
PubMed1997

Predictability of early atopy by cord blood-IgE and parental history.

BACKGROUND: Atopic family history and cord blood IgE have been used as predictors of atopic disease in newborns for about 20 years, but at least for cord blood IgE the sensitivity has been shown to be very low. The objective of this paper was to evaluate whether parental history and cord blood-IgE were more accurate predictors for the appropriate atopic phenotypes in the infants rather than for any atopy. METHODS: A total of 1314 newborn infants was recruited in six German obstetric departments in 1990 and followed-up for 2 years. Four hundred and ninety-nine (38%) were at high risk for atopy with at least two first degree atopic family members and/or elevated cord-blood IgE concentrations. RESULTS: The cumulative incidence of atopic dermatitis over the first 2 years of life (AD24) amounted to 20.1%, and there was a significant association with AD history of the mother (OR 2.5, 95%CI 1.46-4.26) and of the father (OR 3.53, 95%CI 1.90-6.54). The cumulative incidence of recurrent wheezing in the first 2 years of life (RW24) amounted to 16.1%, and was positively associated with asthma history (OR 2.11, 95%CI 1.33-3.60) and sensitization history (OR 1.64, 95%CI 1.34-2.36) of the mother, but with neither for the father. RW24 was less prevalent in girls than in boys (OR 0.64, 95%CI 0.47-0.89). Thirty-one per cent of infants were sensitized (CAP test value > 0.35 kU/L) against at least one of nine food or inhalative allergens (S24) and this was significantly associated with cord blood-IgE value (OR 2.43, 95%CI 1.69-3.49), and sensitization history of the mother (OR 1.64, 95%CI 1.18-2.41). Using multiple logistic regression analysis, the prediction of AD24 by AD of parents, of RW24 by asthma of parents, and of sensitization by cord blood IgE was of low accuracy. CONCLUSION: The predictive capacity of parental history and cord blood IgE is not high enough to recommend them as screening instruments for primary prevention. The majority of atopic manifestations and of sensitization occur in infants with no demonstrable risk at birth.

Adult↗
PubMed1996

CNS complications in a girl with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD).

A 13-year-old girl presented with doughy swelling of both hands, a pruritic maculopapular rash, fever, malaise, lymphadenopathy and splenomegaly. Examination of an enlarged cervical lymph node revealed typical histopathological features of AILD. Partial remission was achieved by treatment with prednisolone. During the next 4 years 3 flare-ups of the disease could be controlled by corticosteroids, one going along with an enlargement of the right tonsil, histologically proven as an AILD manifestation, the other two with generalized lymphadenopathy. At the age of 17 years, an acute reduction of visual acuity occurred in both eyes in the absence of lymphadenopathy or cutaneous manifestations. Plasma viscosity was elevated in connection with high levels of IgM and IgG. Fundoscopy revealed papilledema compatible with hyperviscosity syndrome. Plasmapheresis resulted in a slow recovery of vision when suddenly a bilateral loss of vision occurred. MRI at this time revealed a lesion within the optic chiasm and additional high-signal lesions in parietal white matter of brain. All of these regions showed enhancement after i.v. application of Gd-DTPA. Again, high-dose corticosteroids were introduced and a partial restoration of vision could be achieved. This was paralleled by an improvement of the changes on followup MRI examinations. The last examination ten months after onset of CNS complications revealed a single small hyperintense residual area positioned in left parietal white matter. Enhancement of contrast medium was absent. These cerebral and retinal complications are so far undescribed complications of AILD which occurred in a childhood case.

Adolescent↗