Shaken baby syndrome: report on four pairs of twins.
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Biomedical subjects
Publications and source records attributed to C Tautz.
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A patient is described in whom a large diffuse glioma of the pons extending into the midbrain was diagnosed at the age of 2 years. Biopsy showed a fibrillary astrocytoma. After shunting of a hydrocephalus, the clinical symptoms abated without conventional therapy. Repeated MRI studies showed a continuous decrease of the tumour which was no longer visible when the patient was 6.6 years old. In reviews on spontaneous remissions of oncologic disorders we were unable to find a case of a biologically benign brain stem tumour. There is one isolated report on a similar case, though without histologic documentation.
A panel of 188 unrelated Caucasian subjects who were exposed to the larvae of Chironomus thummi (Diptera, nonbiting midges) was HLA-typed by polymerase chain reaction amplification of the second exons of the DRB, DQA1, and DQB1 genes followed by dot-blot hybridization with sequence-specific oligonucleotide probes. Type I sensitization to the allergen Chi t I and a large number of other inhalant allergens was determined by RAST and skin testing. Sixty-one individuals were found to be sensitized to Chi t I, of whom 24 were sensitive to this allergen and to no other allergens tested. Statistical analyses showed that only in the latter group were the HLA-D genes DRB1*0101, DQA1*0101, and DQB1*0501 associated with IgE-responsiveness to Chi t I. These results suggest that HLA associations with responsiveness to certain allergens may be more striking in monosensitized subjects.
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In Caucasians, HLA-DR2 haplotypes usually express two DRB genes encoding the DR specificity. The DRB5 genes are in strong linkage disequilibrium with the respective DRB1*15 or DRB1*16 alleles. So far, no other DRB1 alleles have been found in association with DRB5 genes. Here, we report evidence for a probably recombinant DRB5 haplotype with a DRB1 allele not specific for DR2. From our results the haplotype DQB1*0501, DRB1*0101 and DRB5*0101 seems most likely.
In this, the first of three papers, we present the sequence of the ribosomal RNA (rRNA) genes of Drosophila melanogaster. The gene regions of D. melanogaster rDNA encode four individual rRNAs: 18S (1,995 nt), 5.8S (123 nt), 2S (30 nt), and 28S (3,945 nt). The ribosomal DNA (rDNA) repeat of D. melanogaster is AT rich (65.9% overall), with the spacers being particularly AT rich. Analysis of DNA simplicity reveals that, in contrast to the intergenic spacer (IGS) and the external transcribed spacer (ETS), most of the rRNA gene regions have been refractory to the action of slippage-like events, with the exception of the 28S rRNA gene expansion segments. It would seem that the 28S rRNA can accommodate the products of slippage-like events without loss of activity. In the following two papers we analyze the effects of sequence divergence on the evolution of (1) the 28S gene "expansion segments" and (2) the 28S and 18S rRNA secondary structures among eukaryotic species, respectively. Our detailed analyses reveal, in addition to unequal crossing-over, (1) the involvement of slippage and biased mutation in the evolution of the rDNA multigene family and (2) the molecular coevolution of both expansion segments and the nucleotides involved with compensatory changes required to maintain secondary structures of RNA.
The organization and sequence of the rDNA multigene family of four Drosophila species (melanogaster, orena, virilis and hydei) have been compared in order to understand the quality and quantity of the differences which are involved with interspecific divergence of promoters and the polymerase I complexes (molecular coevolution). Each species has an intergenic spacer (IGS) made up of subrepeats which contain duplications of the promoter. Major structural and point-mutational differences exist, most of which have been spread by unequal crossingover through the family and species. Structural differences involve the types, lengths and copy-number of the IGS subrepeats, and the lengths and position of "unique" regions between blocks of repeats. The 240 base-pair repeat array shared by D. melanogaster and D. orena has been replaced by a 220 base-pair repeat, and the 95 and 330 base-pair arrays are absent altogether in D. virilis and D. hydei. The length of the "unique" region between the 240/220 base-pair arrays and the start of transcription varies, with the unusual situation of the last of the 220 repeats ending at the external transcribed spacer (ETS) boundary in D. virilis. Other structural differences involve regions of high cryptic simplicity arising from slippage in D. virilis and D. hydei IGSs. Sequence analysis of IGS and the ETSs indicates that the rDNA is not uniformly divergent throughout its length. Apart from the genes, there are regions of relatively high conservation covering the promoter regions and at some but not all potential RNA processing sites. The conserved promoter regions are more extensive within each pair of species D. melanogaster versus D. orena and D. virilis versus D. hydei, in keeping with their phylogenetic distances. Slippage-like mechanisms are involved with large numbers of deletions/insertions that make up the ETS differences between the species. Patterns of shared mutations between IGS subrepeats indicate stages of transition during rDNA differentiation by continual homogenization. The simultaneous operation of different turnover mechanisms, at different periodicities and rates, generates a complex picture of reorganization, some of which would influence the process of molecular coevolution in the family.
A cell-bound hemolytic activity was found in several strains of Serratia marcescens. One Serratia cell per ten erythrocytes was sufficient to cause complete lysis of human erythrocytes within 2 h in the liquid assay. The hemolytic activity resided in the membrane fraction and could be inactivated by incubating cells with proteases. The hemolytic activity was greatly enhanced in actively metabolizing Serratia cells and was partially controlled by the iron supply. Hemolysis was accompanied by degradation of erythrocyte membrane proteins (band 3 and 6, glycophorin) and was independent of the blood group. The exoprotease secreted by S. marcescens in large amounts was not involved in hemolysis. Comparison with various hemolytic strains of Escherichia coli showed that hemolysis of erythrocytes was more pronounced with S. marcescens than with E. coli. In contrast to hemolysis by E. coli, lysis of erythrocytes by S. marcescens was not enhanced by Ca2+ ions.
The electrophoresis mobility test (EM) is credited with an accuracy of 70-90% for the diagnosis of gynaecological malignancies. The test was done in 21 patients with dysplasia of carcinoma in situ of the uterine cervix, 34 patients without malignant or pre-malignant gynaecological findings and 27 women who were not in medical care at the time of the test. The correlation between the EM test and cervical intra-epithelial neoplasia was thus tested. In patients with dysplasia or carcinoma in situ of the cervix the test was positive in over 80%. False positive tests were found in 35% of the patients with non-malignant or pre-malignant gynaecological findings and in 11% of the 27 patients not in medical care. Despite the possibility of regression of the cervical intra-epithelial neoplasia an identical precentage of patients to those with invasive carcinomas of the cervix showed a positive EM test. The density of lymphocytic cells in the dysplastic epithelium of the cervix was also investigated. A correlation between the migration and inhibition in the EM test and the number of lymphocytic cells in the dysplastic epithelium was not found.
A double-blind pilot study of 130 female patients was carried out to determine the feasibility and significance of the EM test in the early diagnosis of carcinoma of the female genital organs and breast. Early stages of cervical carcinoma (carcinoma in situ) as well as fibroid adenoma, mastopathy and breast tumors were tested and compared with the results of their manifest forms. Positive results were recorded in 87.5% of the cases of middle-grade to severe epithelial dysplasia (Papanicolaou III and IV) (n = 10) and in 90% of the cases of carcinoma in situ (n = 16). A positive result in 90% of the cases of carcinoma in situ (n = 16). A positive result in 90% of the cases of genital carcinoma was also recorded. In the case of fibroid adenoma (n = 10) and breast tumor (Prechtel I and II) (n = 16), negative results were recorded in 80.8%, whereas in the manifest forms of carcinoma of the breast a positive result of over 95% was shown. As a result of this pilot study, it can be seen that immunological in vitro screening has clinical significance in the early diagnosis of tumors as well as for confirmation of their manifest forms.
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The lymphocytotoxicity test was used to study the existence of immunologically active lymphocyte reactions in patients with renal carcinoma at different stages. In 9 patients with an advanced renal carcioma (stage IV) a low lymphocytotoxicity was found, while the examination of 7 patients with stage I and II renal tumours showed a high value of the lymphocytotoxicity test. The clinical importance of the lymphocytotoxicity test is discussed with special interest in a possible immunotherapy.
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