Triple sensitization in a child with chronic otitis externa.
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Allergens↗
Biomedical subjects
M Isaksson
Publications and source records attributed to M Isaksson.
Low sex steroid environment affects survival and steroid secretion of ovarian tumour cells in primary cultures.
Ovarian epithelial tumours are considered to be endocrine related. The effects of an environment with low levels of the steroid hormones 17 beta-estradiol, testosterone or progesterone on cell survival and steroid secretion were studied in primary cell cultures derived from 25 patients suffering from epithelial ovarian tumours. Tumour cells cultured in 17 beta-estradiol and testosterone showed a reduced cell survival (-10.3 +/- 2.3% and -15.6 +/- 2.7% minimum survival respectively). This reduction was inversely proportional to hormone concentrations within the range studied. No similar effect was observed in the progesterone cultures. It was found that 17 beta-estradiol was secreted from the primary cell cultures and, interestingly, the amount of 17 beta-estradiol secreted increased with increasing levels of 17 beta-estradiol in the environment. Neither progesterone nor testosterone production was observed in any of the cultures studied. It is believed that 17 beta-estradiol has an antiapoptotic effect on ovarian surface epithelial (OSE) cells. Reduction of 17 beta-estradiol in the environment may inhibit this effect, resulting in reduced cell survival. The ability of ovarian epithelial tumour cells to secrete 17 beta-estradiol suggests that epithelial ovarian tumours play an active role in altering their own hormonal environment, promoting tumour progression.
Adult↗
Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid leukemias with the t(7;12)(q36;p13).
Recently, we and others reported a recurrent t(7;12)(q36;p13) found in myeloid malignancies in children < or =18 months of age and associated with a poor prognosis. Fluorescence in situ hybridization studies mapped the 12p13 breakpoint to the first intron of ETV6 and narrowed down the region of 7q36 involved. By using the sequences made public recently by the Human Genome Project, two candidate genes in 7q36 were identified: the homeobox gene HLXB9 and c7orf3, a gene with unknown function. Reverse transcription-PCR of two cases with t(7;12), using primers for c7orf3 and ETV6, was negative. However, reverse transcription-PCR for HLXB9-ETV6 demonstrated alternative splicing; the two major bands corresponded to fusion of exon 1 of HLXB9 to exons 2 and 3, respectively, of ETV6. The reciprocal ETV6-HLXB9 transcript was not detected. It remains to be elucidated if the leukemic phenotype is attributable to the formation of the HLXB9-ETV6 fusion protein, which includes the helix-loop-helix and E26 transformation-specific DNA binding domains of ETV6 or to the disruption of the normal ETV6 protein.
Acute Disease↗
Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13).
The CBP gene at 16p13 fuses to MOZ and MLL as a result of the t(8;16)(p11;p13) in acute (myelo)monocytic leukemias (AML M4/M5) and the t(11;16)(q23;p13) in treatment-related AML, respectively. We show here that a novel t(10;16)(q22;p13) in a childhood AML M5a leads to a MORF-CBP chimera. RT-PCR using MORF forward and CBP reverse primers amplified a MORF-CBP fusion in which nucleotide 3103 of MORF was fused in-frame with nucleotide 284 of CBP. Nested RT-PCR with CBP forward and MORF reverse primers generated a CBP-MORF transcript in which nucleotide 283 of CBP was fused in-frame with nucleotide 3104 of MORF. Genomic analyses revealed that the breaks were close to Alu elements in intron 16 of MORF and intron 2 of CBP and that duplications had occurred near the breakpoints. A database search using MORF cDNA enabled us to construct an exon-intron map of the MORF gene. The MORF-CBP protein retains the zinc fingers, two nuclear localization signals, the histone acetyltransferase (HAT) domain, a portion of the acidic domain of MORF and the CBP protein downstream of codon 29. Thus, the part of CBP encoding the RARA-binding domain, the CREB-binding domain, the three Cys/His-rich regions, the bromodomain, the HAT domain and the Glu-rich domains is present. In the reciprocal CBP-MORF, part of the acidic domain and the C-terminal Ser- and Met-rich regions of MORF are likely to be driven by the CBP promoter. Since both fusion transcripts were present, their exact role in the leukemogenic process remains to be elucidated.
Acetyltransferases↗
Clinical impact of molecular and cytogenetic findings in synovial sarcoma.
Synovial sarcoma is an aggressive soft-tissue tumor that accounts for up to 10% of soft-tissue sarcomas. Cytogenetically, synovial sarcoma is characterized by the t(X;18)(p11;q11), found in more than 95% of the tumors. This translocation results in rearrangements of the SYT gene in 18q11 and one of the SSX1, SSX2, or SSX4 genes in Xp11, creating a SYT/SSX1, SYT/SSX2, or SYT/SSX4 chimeric gene. It has been shown that patients with SYT/SSX1 fusion genes have a shorter metastasis-free survival than do patients with SYT/SSX2. Previous studies have also suggested that clonal evolution may be associated with disease progression. In the present study, RT-PCR analysis showed that all 64 examined synovial sarcomas from 54 patients had SYT-SSX chimeric genes. SYT/SSX1 was found in 40 tumors from 33 patients, SYT/SSX2 in 23 tumors from 20 patients, and SYT/SSX4 in one case. Two patients had variant SYT/SSX2 transcripts, with 57 bp and 141 bp inserts, respectively, between the known SYT and SSX2 sequences. Patients with tumors with SYT/SSX1 fusions had a higher risk of developing metastases compared to those with SYT/SSX2 fusions (P = 0.01). The reciprocal transcripts SSX1/SYT and SSX2/SYT were detected using nested PCR in 11 of the 40 samples with SYT/SSX1 and 5 of the 23 samples with SYT/SSX2, respectively. Among 20 blood samples, SYT/SSX1 and SYT/SSX2 were detected in one sample each. The t(X;18), or variants thereof, was found cytogenetically in all patients but three. Among 32 primary tumors, the t(X;18) or a variant translocation was the sole anomaly in 10. In contrast, of the seven metastatic lesions that were investigated prior to radiotherapy, only one had a t(X;18) as the sole anomaly; all other tumors displayed complex karyotypes. Cytogenetic complexity in primary tumors was, however, not associated with the development of metastases. Tumors with SYT/SSX2 less often (4/12 vs. 7/15) showed complex karyotypes than did tumors with SYT/SSX1, but the difference was not significant. Combining cytogenetic complexity and transcript data, we found that the subgroup of patients with tumors showing simple karyotypes and SYT/SSX2 fusion had the best clinical outcome (2/8 patients developed metastases), and those with tumors showing complex karyotypes together with SYT/SSX1 fusion the worst (6/7 patients developed metastases). This corresponded to 5-year metastasis-free survival rates of 0.58 and 0.0, respectively (P = 0.02).
Adolescent↗
Fusion of the BCR and the fibroblast growth factor receptor-1 (FGFR1) genes as a result of t(8;22)(p11;q11) in a myeloproliferative disorder: the first fusion gene involving BCR but not ABL.
Constitutive activation of tyrosine kinases as a consequence of chromosomal translocations, forming fusion genes, plays an important role in the development of hematologic malignancies, in particular, myeloproliferative syndromes (MPSs). In this respect, the t(9;22)(q34;q11) that results in the BCR/ABL fusion gene in chronic myeloid leukemia is one of the best-studied examples. The fibroblast growth factor receptor 1 (FGFR1) gene at 8p11 encodes a transmembrane receptor tyrosine kinase and is similarly activated by chromosomal translocations, in which three alternative genes-ZNF198 at 13q12, CEP110 at 9q34, and FOP at 6q27-become fused to the tyrosine kinase domain of FGFR1. These 8p11-translocations are associated with characteristic morphologic and clinical features, referred to as "8p11 MPS." In this study, we report the isolation and characterization of a novel fusion gene in a hematologic malignancy with a t(8;22)(p11;q11) and features suggestive of 8p11 MPS. We show that the breakpoints in the t(8;22) occur within introns 4 and 8 of the BCR and FGFR1 genes, respectively. On the mRNA level, the t(8;22) results in the fusion of BCR exons 1-4 in-frame with the tyrosine kinase domain of FGFR1 as well as in the expression of a reciprocal FGFR1/BCR chimeric transcript. By analogy with data obtained from previously characterized fusion genes involving FGFR1 and BCR/ABL, it is likely that the oligomerization domain contributed by BCR is critical and that its dimerizing properties lead to aberrant FGFR1 signaling and neoplastic transformation.
Aged↗
No EWS/FLI1 fusion transcripts in giant-cell tumors of bone.
Giant-cell tumor of bone (GCT) is a locally aggressive neoplasm of unknown etiology and pathogenesis. Cytogenetically, no consistent chromosomal alterations, apart from telomeric associations involving various chromosome ends, have been described. Recently, however, it was reported that by using highly sensitive nested RT-PCR, a high proportion of GCT displays chimeric EWS/FLI1 fusion transcripts, i.e., the molecular genetic feature previously known to be strongly associated with the Ewing family of tumors. Thus, we decided to perform single-step and nested RT-PCR analyses on fresh frozen samples from 10 cases of GCT, all of which had also been subjected to cytogenetic analysis. After short-term culturing, none of the samples displayed any t(11;22)(q24;q12), the translocation characteristically giving rise to the EWS/FLI1 fusion, nor any other type of rearrangement of 11q24 or 22q12. Furthermore, in none of the cases did the RT-PCR analysis, whether single step or nested, result in products corresponding to a hybrid EWS/FLI1 transcript. On the basis of these results, we conclude that translocations leading to fusion of the EWS and FLI1 genes are not part of the pathogenesis of GCT.
Adult↗
A 10-year study of the 137Cs distribution in soil and a comparison of Cs soil inventory with precipitation-determined deposition.
During a 10-year period, 1988-1998, surface soil samples have been collected at Blentarp in southern Sweden and analysed for 137Cs from the Chernobyl accident and from the nuclear weapons tests. The distance between the sampling plots on the different sampling occasions has been no more than 3 m. The results show that the depth distribution of 137Cs is very similar for each of the sampling occasions, indicating that the caesium migration at this site is very small. The total activity measured in the soil cores is in agreement with the calculated activity of 137Cs deposited at the site after nuclear weapons tests and the Chernobyl accident, based on air activity concentration and the amount of precipitation. The calculated deposition of 137Cs originating from the bomb tests amounts to 1.41 kBq m-2 for the period 1962-1986, which is in agreement with the activity of nuclear weapons fallout measured in the soil samples (1.60 kBq m-2 as a mean value of the first four years of sampling). The calculated activity of 137Cs of Chernobyl origin was 0.79 kBq m-2, which agrees well with the value of 0.79 kBq m-2 measured in the soil samples in 1988.
Cesium Radioisotopes↗
Repetitive usage testing with budesonide in experimental nickel--allergic contact dermatitis in individuals hypersensitive to budesonide.
BACKGROUND: Contact allergy to topical corticosteroids on patch testing is well recognized, but the clinical significance is uncertain. OBJECTIVES: To determine the clinical relevance of contact allergy to topical corticosteroids. METHODS: Seven patients hypersensitive to both budesonide and nickel repeatedly applied budesonide, betamethasone valerate or the common base for both corticosteroids to areas of experimentally induced nickel dermatitis. Nineteen controls allergic to nickel, but not budesonide went through the same procedure. RESULTS: Seventy-one per cent of the budesonide-allergic individuals experienced distant ipsilateral flares of toxicoderma-like eruptions, in addition to a severe deterioration of the experimental dermatitis treated with budesonide, i.e. increased erythema, and abundant papules and vesicles. The areas of dermatitis in all of the 19 controls healed uneventfully. CONCLUSIONS: The clinical relevance of a contact allergy to budesonide was thus substantiated.
Administration, Topical↗
Skin reactions to inhaled corticosteroids.
Corticosteroids intended for inhalation into the lungs or into the nose have been used since the 1970s. Only 2 attempts to assess contact allergy attributable to inhaled corticosteroids in patients with asthma and/or rhinitis have been made, and only 1 single case of contact allergy attributable to budesonide and tixocortol pivalate was found. However, several case reports of allergic mucosal and skin symptoms caused by corticosteroids applied locally to the mucosa have been published. Local adverse effects from nasal corticosteroids have ranged from nasal congestion, pruritus, burning, and soreness to perforation of the nasal septum. Inhalation of corticosteroids into the lungs has been reported to cause pruritus, dryness, erythema and oedema of the mouth, a dry cough and odynophagia. Systemic signs reported from the use of nasal corticosteroids and inhalation of corticosteroids into the lungs have been eczematous lesions, particularly on the face, sometimes with spreading to the trunk and flexures. Urticaria has also been noted.
Administration, Inhalation↗
Patch testing with serial dilutions of budesonide, its R and S diastereomers, and potentially cross-reacting substances.
BACKGROUND: Budesonide, a marker for corticosteroid allergy, is a 1:1 mixture of 2 diastereomers, the R and S, present in all commercial formulations. Budesonide is said to cross-react with group B substances through the R and S diastereomer and some group D substances only through the S diastereomer. OBJECTIVE: To investigate the cross-reactivity pattern between the R and S diastereomers and 4 potentially cross-reacting substances, 2 from group B and 2 from group D. METHODS: By patch testing 10 patients hypersensitive to budesonide with a serial dilution of budesonide, the R and S diastereomer, triamcinolone acetonide, amcinonide, prednicarbate, and hydrocortisone-17-butyrate. RESULTS: Nine of 10 patients reacted to budesonide and the S diastereomer. Seven of 9 to the R diastereomer. Each of the 9 patients with S diastereomer allergy reacted to the group B and/or group D substances. Five patients reacted to triamcinolone acetonide, not to 1.0% but only to 0.0010% and 0.00010%. CONCLUSION: The R and S diastereomers can induce positive patch test reactions in budesonide-hypersensitive individuals. The potential of budesonide to cross-react with substances from group B and D might be explained by the presence of the 2 diastereomers. When patch testing with triamcinolone acetonide, much lower concentrations than recommended should be used.
Allergens↗
A novel FUS/CHOP chimera in myxoid liposarcoma.
The cytogenetic hallmark of myxoid liposarcoma is the chromosomal aberration t(12;16)(q13;p11), which is pathognomonic for this tumor type. The translocation results in the hybrid gene FUS/CHOP, where the central and C-terminal parts of FUS, coding for the RNA binding domain and the RGG triplet motif, are replaced by the full length CHOP protein. Thus, CHOP is under the control of the FUS promoter and the FUS/CHOP chimera contains the 5'-terminal part of FUS which provides a transcriptional activation function. Although different structural variations of the FUS/CHOP chimeric transcript have been reported, none of them contains the parts of FUS encoding the RNA binding properties. An explanation is the location of the genomic breakpoint in FUS, which frequently occurs in the region spanning exon 5 to intron 8. We describe here a case of myxoid liposarcoma containing two novel FUS/CHOP chimeric transcripts and with the breakpoint occurring in intron 14 of FUS. Reverse transcription-polymerase chain reaction, using FUS forward and CHOP reverse primers, amplified strongly a 2.1-kbp DNA fragment and weakly a 0.9-kbp DNA fragment. Direct sequencing showed that in the 2.1-kbp transcript nt 1474, which corresponds to the third nucleotide of exon 14 of FUS, was in-frame fused to exon 2 of CHOP. In the 0.9-kbp DNA fragment, exon 3 of FUS was in-frame fused to exon 2 of CHOP. Genomic analyses revealed that the breaks were located at the end of exon 14/beginning of intron 14 of FUS and in intron 1 of CHOP and that microdeletions had occurred in the close vicinity of the breakpoints.
Amino Acid Sequence↗
RT-PCR analysis of the MOZ-CBP and CBP-MOZ chimeric transcripts in acute myeloid leukemias with t(8;16)(p11;p13).
The translocation t(8;16)(p11;p13) is associated with a subtype of acute monocytic leukemia (AML M5) characterized morphologically by erythrophagocytosis and clinically by a poor prognosis. The t(8;16) fuses the MOZ gene from 8p11 with the CBP (also named CREBBP) gene from 16p13. Previously published studies of MOZ and CBP rearrangements in t(8;16)-positive AML have used fluorescence in situ hybridization and Southern blot methodologies, whereas attempts to amplify and to analyze further the chimeric MOZ-CBP and CBP-MOZ transcripts by means of reverse transcriptase-polymerase chain reaction (RT-PCR) have largely been unsuccessful. In the only t(8;16) that has been described at the sequence level using RT-PCR, the CBP-MOZ fusion was found to be out-of-frame, suggesting that the reciprocal MOZ-CBP transcript is the essential one for leukemogenesis. We have developed an RT-PCR strategy that enables us to detect the MOZ-CBP as well as the CBP-MOZ fusions in the two AML M5 with t(8;16)(p11;p13) analyzed. In both leukemias, the combination of a MOZ forward and a CBP reverse primer amplified a strongly expressed 1,128 bp fragment (type I transcript) and a weakly expressed 415 bp fragment (type II transcript). In the type I transcript, nucleotide (nt) 3,745 of MOZ was fused in-frame with nt 284 of CBP, whereas in the type II transcript, nt 3,745 of MOZ was fused out-of-frame with nt 997 of CBP. Nested PCR with a combination of two forward CBP and two reverse MOZ primers amplified CBP-MOZ chimeric transcripts in both cases. Direct sequence analysis showed that nt 283 of CBP was fused in-frame with nt 3,746 of MOZ, that the initiation ATG codon of the CBP gene remained intact, and that there was no mutation or deletion in the part of the CBP gene included in the CBP-MOZ transcript. Thus, the data we present are not informative with regard to the question whether it is the MOZ-CBP or the CBP-MOZ transcript that is leukemogenic. The present RT-PCR method may be of value for rapid identification of the t(8;16) and also for further molecular genetic studies of the two fusion transcripts and their roles in leukemogenesis.
Acetyltransferases↗
Determination of the retention of 47Ca by whole-body counting.
Retention of intravenously or orally administered 47Ca in the human body are described by a two-parameter function. It is then sufficient to make only a few whole-body measurements to determine the retention function, avoiding faeces sampling and stool markers. Seven days after intake the non-absorbed calcium was excreted and the model agreed with the measured relative retention. Absorption of calcium could then, in some cases (e.g. comparative studies), be described by relative retention at the 7th day after intake.
Adult↗
Patch testing with corticosteroid mixes in Europe. A multicentre study of the EECDRG.
This study investigated whether a corticosteroid mix containing tixocortol pivalate, budesonide, and hydrocortisone-17-butyrate could detect contact allergy to corticosteroids. 2 corticosteroid mixes, 1 with a high (mix I) and 1 with a low (mix II) concentration and the 3 individual constituents, each at 2 concentrations, were inserted into the standard series of 16 participating clinics. Tests were read on day (D) 3 or 4. 5432 patients were tested, and 110 (2.0%) had positive reactions to at least 1 of the 8 test preparations. Of the 8 preparations, mix I identified most allergic patients, followed by mix II, budesonide 0.10%, budesonide 0.002%, and tixocortol pivalate, both concentrations (1.0 and 0.10%) tracing the same number. With the mixes, 53.2-59.6% of tixocortol pivalate allergy was missed. 47 patients were allergic to either concentration of tixocortol pivalate, 25% of these only to 1.0% and another 25% only to 0.10%. Testing with mix I and tixocortol pivalate 0.10% picked up 98/110, testing with tixocortol pivalate 1.0% and 0.10% and budesonide 0.10% picked up 105/110. 3379 patients were read on both D3 or D4 as well as on D7. Without a late reading (D7), up to 30% of contact allergy to corticosteroid markers was missed.
Administration, Topical↗
Stability of corticosteroid patch test preparations.
This study investigated the stability of tixocortol pivalate, budesonide, and hydrocortisone-17-butyrate (Hc-17-B) when present in a mix with petrolatum and when the corticosteroids were kept separately in petrolatum. The concentrations chosen for the corticosteroids were the same as those used in a study within the European Environmental Contact Dermatitis Research Group (EECDRG), in which 2 corticosteroid mixes (1 with a high concentration and 1 with a low concentration) and the 3 individual constituents, each at 2 concentrations, were patch tested. Ethanolic solutions of each corticosteroid, as well as 2 mixtures of these 3 corticosteroids, were also made up at corresponding concentrations. The preparations were kept at room temperature, refrigerated, and deep frozen, and repeatedly for 1 year, investigations to check stability by high performance liquid chromatography were carried out. A decrease of < or =20% of the initial value at time 0 was used as the threshold for stability. The petrolatum preparations and the ethanolic solutions of budesonide and tixocortol pivalate were stable for at least the whole investigative period, irrespective of storage conditions, while Hc-17-B 1.0% in ethanol kept deep frozen was stable at least during the same period. The latter corticosteroid when kept at room temperature was stable for 3 months only.
Administration, Topical↗
Recommendation to include budesonide and tixocortol pivalate in the European standard series. ESCD and EECDRG. European Society of Contact Dermatitis.
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Administration, Topical↗
Regular disappearance of the human papillomavirus genome after conization of cervical dysplasia by carbon dioxide laser.
OBJECTIVE: We wished to evaluate the effectiveness of treatment of cervical dysplasia by laser conization in relation to persistence of human papillomavirus after treatment. STUDY DESIGN: Of 203 women referred to colposcopy because of an abnormal Papanicolaou smear, 149 women could be followed up for 3 years. A total of 108 women were treated by carbon dioxide laser excision, 4 women were treated by carbon dioxide laser evaporation, and 37 women were merely followed up. Cervical samples were taken before treatment and at follow-up 3 years later and were analyzed by nested general primer polymerase chain reaction for human papillomavirus deoxyribonucleic acid. RESULTS: Among women treated by laser conization, 82 (73.2%) had positive results for human papillomavirus deoxyribonucleic acid before treatment. Three women (2.7%) had a positive finding at follow-up, but no woman had the same human papillomavirus type on both occasions. Eighty-eight women had grade 1 to grade 3 cervical intraepithelial neoplasia before treatment, whereas during follow-up only 2 squamous cells atypias were found. CONCLUSION: The human papillomavirus genome present before treatment was regularly cleared, and there was also no recurrence of dysplasia. The results suggest that human papillomavirus testing is useful for monitoring the efficacy of treatment and that treatment modalities resulting in clearance of human papillomavirus should be favored.
Adult↗