Sero- and subtypes of group B meningococci causing invasive infections in Finland in 1976-87

Neisseria meningitidis group B (MenB) strains isolated from 1976 to 1987 in Finland in 339 patients with invasive infection were sero/subtyped by whole cell enzyme immunoassay using monoclonal antibodies to class 1 and 2/3 outer membrane proteins. 66.7% of the strains could be serotyped (class 2/3) and 70.2% subtyped (class 1). No single phenotype was clearly predominant. The most common serotypes were 4 (18.6%) and 14 (17.4%) and the most common subtypes P1.16 (20.1%) and P1.2 (12.1%). The Norwegian phenotype B:15:P1.16 was seen only rarely (a total of 18 strains). Strains from Northern Finland did not differ from those from Southern Finland: no single phenotype caused the slight increase seen in the incidence of MenB infections in the end of 1970s in the North.     

Fracture repair during external fixation: Torsion tests of rabbit osteotomies

Bone repair was studied in the rabbit tibiofibular bone after a midshaft transverse osteotomy stabilized by external fixation and heavy compression. Both subendosteal and subperiosteal callus formation with concomitant contact healing were observed within 3 weeks, and were further succeeded by subendosteal resorption and increased porosis resulting in atrophy of the cortical bone. Subjected to the torsion test, the bones exhibited restoration of strength within 3 weeks, with maximal energy absorption and elasticity at 6 weeks. The failure of the osteotomy in the torsion test, with radiographic visibility of the osteotomy, characterized the soft-tissue type of behavior of the bones. Hard-tissue like behaviour of the bones with resistance to torsion at the osteotomy site and radiographic obliteration of the osteotomy line occurred by 12 weeks, indicating complete union of the osteotomy. Our experiments demonstrate that elastic external fixation is preferable to the rigid compression plate.     

Recombinant allergen fragments as candidate preparations for allergen immunotherapy

Background: Lately, renewed interest has arisen in the new forms of allergen immunotherapy because they may offer alternatives for drug treatment. Objective: The purpose of this study was to develop a well-characterized preparation of the main respiratory cow dander allergen, Bos d 2, with attenuated allergenic activity. Methods: The immunologic characteristics of Bos d 2 preparations were studied by indirect IgE ELISA, ELISA inhibition, Western blotting, histamine release, skin prick tests, and the proliferation tests of allergen-specific T-cell clones. Results: The complete recombinant Bos d 2 was observed to bind effectively, IgE of cow-allergic patients in indirect ELISA. In other experiments, the IgE-binding capacity of recombinant Bos d 2 proved to be lower compared with native Bos d 2. When the two overlapping recombinant fragments of Bos d 2 (corresponding amino acids 1-131 and 81-172, respectively) covering the whole molecule were compared with the complete recombinant Bos d 2 with several methods, only a low level of residual reactivity was observed. For example, recombinant fragments could not bind antibody at all in ELISA inhibition tests retaining, however, some reactivity in skin prick tests. In contrast, the fragments were able to stimulate vigorously Bos d 2-specific T-cell clones. Conclusion: The approach we have taken may offer a simple and reproducible way to produce hypoallergenic preparations for immunotherapy, circumventing simultaneously some of the problems of other experimental methods such as individual T-cell epitope recognition in peptide-based immunotherapy. (J Allergy Clin Immunol 1997;100:721-7.)     

Improved learning of Riemannian metrics for exploratory analysis.

We have earlier introduced a principle for learning metrics, which shows how metric-based methods can be made to focus on discriminative properties of data. The main applications are in supervising unsupervised learning to model interesting variation in data, instead of modeling all variation as plain unsupervised learning does. The metrics are derived by approximations to an information-geometric formulation. In this paper, we review the theory, introduce better approximations to the distances, and show how to apply them in two different kinds of unsupervised methods: prototype-based and pairwise distance-based. The two examples are self-organizing maps and multidimensional scaling (Sammon's mapping).     

Inheritance of male courtship sound characteristics inDrosophila littoralis

Males ofDrosophila littoralis vibrate their wings during courtship to deliver a love song. This consists of 25- to 50-ms-long pulses with a basic frequency of about 250–400 Hz, separated by 250- to 500-ms pauses. When recording the sounds of flies from several localities in Europe, we found that males of one strain from northern Finland displayed courtship sounds with an unusally low wing beat frequency (below 250 Hz). In a genetic analysis utilizing marker stocks, the anomalous frequency was found to be caused by genes on all major autosomes, the strongest factors being on the second chromosome. Interaction between genes on chromosome 2 and on the fused chromosome 3–4 was nonadditive. In low-frequency sounds, the number of cycles in the pulse (CN) was decreased, so that the length of the sound pulse (PL) remained more or less unchanged. We suggest that the genetically and physiologically most thoroughly controlled trait in the sound ofDrosophila littoralis is the length of the pulse.     

Array comparative genomic hybridization analysis of olfactory neuroblastoma.

Olfactory neuroblastoma is an unusual neuroectodermal malignancy, which is thought to arise at the olfactory membrane of the sinonasal tract. Due to its rarity, little is understood regarding its molecular and cytogenetic abnormalities. The aim of the current study is to identify specific DNA copy number changes in olfactory neuroblastoma. Thirteen dissected tissue samples were analyzed using array comparative genomic hybridization. Our results show that gene copy number profiles of olfactory neuroblastoma samples are complex. The most frequent changes included gains at 7q11.22-q21.11, 9p13.3, 13q, 20p/q, and Xp/q, and losses at 2q31.1, 2q33.3, 2q37.1, 6q16.3, 6q21.33, 6q22.1, 22q11.23, 22q12.1, and Xp/q. Gains were more frequent than losses, and high-stage tumors showed more alterations than low-stage olfactory neuroblastoma. Frequent changes in high-stage tumors were gains at 13q14.2-q14.3, 13q31.1, and 20q11.21-q11.23, and loss of Xp21.1 (in 66% of cases). Gains at 5q35, 13q, and 20q, and losses at 2q31.1, 2q33.3, and 6q16-q22, were present in 50% of cases. The identified regions of gene copy number change have been implicated in a variety of tumors, especially carcinomas. In addition, our results indicate that gains in 20q and 13q may be important in the progression of this cancer, and that these regions possibly harbor genes with functional relevance in olfactory neuroblastoma.     

CDK4 is a probable target gene in a novel amplicon at 12q13.3-q14.1 in lung cancer

Several chromosomal regions are recurrently amplified or deleted in lung tumors, but little is known about the underlying genes, which could be important mediators in tumor formation or progression. In lung cancer, the RB1-CCND1-CDKN2A pathway, involved in the G1-S transition, is damaged in nearly all tumors. In the present study, we localized a novel amplicon in lung tumors to a fragment of less than 0.5 Mb at 12q13.3-q14.1 by using comparative genomic hybridization (CGH) on cDNA microarrays. This approach enabled us to identify 10-15 genes with the most consistent amplifications. Semiquantitative RT-PCR analyses of 13 genes in this region showed that four of them (CDK4, CYP27B1, METTL1, and TSFM) were also highly up-regulated. Immunohistochemical (IHC) analysis of 141 tumor samples on a tissue microarray showed that CDK4 was expressed at a high level in 23% of lung tumors. Six (21.4%) of the tumors with high CDK4 expression (n = 28) were shown by fluorescence in situ hybridization (FISH) to contain the 12q13.3-q14.1 amplification. For CDK4, a positive correlation was found between gene copy number (FISH and CGH array), mRNA expression (RT-PCR), and level of protein expression (IHC). CDK4 expression did not correlate with CDKN2A methylation status. Amplification of CDK4 has been described in other tumor types, but its role in lung cancer remains to be elucidated. Although CDK4 amplification seems to be a relatively rare event (4.3%) in lung tumors, it indicates the significance of the RB1-CCND1 pathway in lung tumorigenesis.