Anomalies of digastric muscles: CT and MR demonstration

Anomalies of the anterior bellies of the digastric muscles were described during the 19th century and have been of little clinical significance. However, new imaging modalities, such as ultrasound, CT, and magnetic resonance (MR) imaging, can easily depict muscle anatomy without having to rely on dissection studies. The anterior bellies of the digastric muscles were evaluated in 40 patients having CT and 35 patients having MR imaging of the oropharynx. An accessory muscle crossing the midline between two normal digastric muscles was found in a patient in the MR imaging group. In the CT group, one patient showed absence of one anterior belly; in its place a small muscle was seen passing from the hyoid bone to the midline raphe of the mylohyoid muscle. It is necessary to recognize that muscle variants of the digastric muscle occur, to avoid confusion with abnormal lesions of the floor of the mouth and the submental space.     

Excitability in free muscle transfers: an optimal method of monitoring tissue circulation?

Recent methods of postoperative monitoring of free muscle transfers were used in 4 patients operated on with free revascularized gracilis muscle. The contractility/electromyographic (EMG) activity in response to electrical stimulation was used as an index of viability, i.e., intact circulation. However, during operations it was observed that contractions as well as EMG potentials could be evoked 1 to 2 hours after blood flow had been arrested. Muscle excitability was further studied in the gracilis muscle from a patient who had undergone hemipelvectomy; it was found that contractility and EMG potentials were evoked at least 4 hours after circulatory arrest. It thus seems that loss of muscle excitability is not as early a sign of impaired blood supply as recently has been suggested. Spontaneous EMG activity, which can be recorded 2 to 3 weeks after denervation, is reported to be affected earlier than muscle excitability by circulatory arrest. Thus, the recording of spontaneous EMG activity in previously denervated muscles is proposed as an alternative and simple electrophysiological method for post-operative monitoring of vascularization in free muscle transfers.     

Pleural mesotheliomas and asbestos exposure in the pulp and paper industries: a new risk group identified by linkage of official registers

Analysis of data obtained by linking the 1960 Swedish Census and the Swedish Cancer Registry has demonstrated an increased risk of pleural mesothelioma among pulp and paper workers. The present study was undertaken with the aim of revealing possible environmental risk factors. The work histories of the 25 cases identified earlier were reviewed. "Certain" or "probable" exposure to asbestos was found among 70% of these workers. The study illustrates how linkage of official registers can be used to identify new risk environments and encourage the establishment of preventive measures.     

Structural and functional aspects of platelet-derived growth factor and its role in the pathogenesis of glioblastoma

The platelet-derived growth factor (PDGF) family consists of three different dimeric forms, AA, BB, and AB, of the two consitituent polypeptide chains, A and B. These interact with two different cell surface receptors that, in part, mediate different cellular functions. The various forms of PDGF, as well as the receptors, are expressed at high frequency in glioblastoma multiforme, and it has been suggested that the growth of this tumor might be affected by autocrine loops involving PDGF and its receptors. The present paper focuses on recent discoveries regarding the family of PDGF ligands and receptors, as well as reviews results concerning PDGF-dependent autocrine growth in experimental and spontaneous glioblastoma.     

Effects of glutathione transferase activity on benzo[a]pyrene 7,8-dihydrodiol metabolism and mutagenesis studied in a mammalian cell co-cultivation assay

This study deals with the role of glutathione transferase (GST)-mediatedconjugation of (+)-7ß,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene(BPDE) in two mammalian cell lines, human mammary carcinomacells (MCF-7) and rat hepatoma cells (H4IIE), in relation tothen-capacity to metabolize (–)-trans-7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene[(–)-BP-7,8-diol] to products that induce mutations inco-cultivated V79 cells. Both MCF-7 and H4IIE cells metabolized(–)-BP-7,8-diol to BPDE, but mutations in co-cultivatedV79 cells were only detected with MCF-7 cells. However, depletionof glutathione (GSH) in H4HE cells increased the mutagenidtyof (– )-BP-7,8-diol to a similar level to that found withMCF-7 cells. Measurements of GST activity using GSH and post-microsomalsupernatants from H4IIE, V79 and MCF-7 cells indicated a substantialdifference in conjugation capacity. Although preparations fromall three cell-lines showed GST activity with l-chloro-2,4-dlnitro-benzeneas the substrate, GST activity towards BPDE could only be detectedin supernatants from H4HE cells. This is consistent with thepresence of GST 7-7 an isoenzyme highly efficient hi catalysingBPDE-GSH conjugation. The difference in GSH-conjugation activitytowards BPDE was confirmed using intact H4IIE and MCF-7 cellsin culture. These results indicate that GSH-conjugation playsa pivotal role in mutagenesis induced by polycyclk aromatichydrocarbons (PAH). Accordingly, a deficiency in GSH-conjugationcapacity may be regarded as one important factor in defininga target cell population with an increased risk for tumour initiationfollowing exposure to PAH.     

Identification and characterization of clonal NK-like cells from channel catfish (Ictalurus punctatus)

TcR alpha, beta, and gamma chain negative cytotoxic NK-like cells were cloned from alloantigen-stimulated PBL obtained from nai;ve channel catfish. Stimulation with allogeneic cells and growth promoting factors are required for their continued in vitro proliferation and cytotoxic activity. These granular cells kill not only the stimulating allogeneic cells, but also unrelated allogeneic targets by a perforin/granzyme-mediated apoptosis pathway. In addition, they are negative for markers that define neutrophils, monocytes/macrophages, and non-specific cytotoxic cells. Although these NK-like clones kill a number of different allogeneic targets, they display interclonal variation in cytotoxicity toward a panel of allogeneic targets, i.e. some clones have no apparent target specificity, while others display a target preference. In addition, flow cytometric analyses revealed that expression of a putative FcmuR, an LFA-1-like molecule, and a putative thymocyte/T cell antigen varies among the different clones, with no clear correlation between surface antigen expression and cytotoxic activity. Although not all clones express a putative FcmuR, it was noted that they all expressed an ITAM containing FcepsilonR gamma chain homolog. This finding suggests that the catfish FcepsilonR gamma chain may potentially be used as an accessory molecule for not only FcmuRs, but also for other unknown activation receptors. These results support the hypothesis that catfish NK-like cells are heterogeneous in terms of target specificities and cell surface phenotype.     

Increased NADPH-diaphorase activity in canine myxomatous mitral valve leaflets

Comparable pathological changes in the mitral valve have been described in dogs, pigs and human patients with myxomatous mitral valve disease (MMVD), i.e., primary mitral valve prolapse. The progressive myxomatous changes are probably a response to repeated impact on the leaflets, and endothelial stress or damage probably plays a central role in the pathogenesis. Little, however, is known about the vasoactive substances that mediate the subendothelial changes. The aim of this study was to investigate the expression of nitric oxide synthase (NOS) in canine mitral valve leaflets and to relate the findings to MMVD changes. The mitral valve was taken post mortem from 12 dogs (six males and six females) and a whole valve NADPH (the reduced form of nicotinamide-adenine dinucleotide phosphate) diaphorase (NADPH-d) reaction was performed. Macroscopical (semiquantitative) and microscopical (computer image analysis) evaluations of the staining due to NADPH-d activity were performed at four specific areas of the valve and related to microscopical signs of MMVD and gross signs of thickening or prolapse, or both. Macroscopically, the NADPH-d colour grade was correlated with the degree of MMVD (P=0.01). In addition, endothelial NADPH-d staining intensity was correlated with macroscopical signs of disease (P=0.004) as well as with collagen degeneration (P=0.008) and deposition of mucopolysaccharides (P=0.02). Age, gender and specific area of the valve did not seem to influence the NADPH-d activity. In conclusion, increased NADPH-d activity, suggesting increased NOS expression, was found in areas of the mitral valve with myxomatous changes. This indicates that nitric oxide (NO) may play a role in the pathogenesis of MMVD in dogs.     

Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy

The purpose of this work is to evaluate the predictive strength of the relative seriality, parallel and LKB normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis, in a large group of patients following breast cancer radiotherapy, and furthermore, to illustrate statistical methods for examining whether certain published radiobiological parameters are compatible with a clinical treatment methodology and patient group characteristics. The study is based on 150 consecutive patients who received radiation therapy for breast cancer. For each patient, the 3D dose distribution delivered to lung and the clinical treatment outcome were available. Clinical symptoms and radiological findings, along with a patient questionnaire, were used to assess the manifestation of radiation-induced complications. Using this material, different methods of estimating the likelihood of radiation effects were evaluated. This was attempted by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Additionally, the need for an update of the criteria that are being used in the current clinical practice was also examined. The patient material was selected without any conscious bias regarding the radiotherapy treatment technique used. The treatment data of each patient were applied to the relative seriality, LKB and parallel NTCP models, using published parameter sets. Of the 150 patients, 15 experienced radiation-induced pneumonitis (grade 2) according to the radiation pneumonitis scoring criteria used. Of the NTCP models examined, the relative seriality model was able to predict the incidence of radiation pneumonitis with acceptable accuracy, although radiation pneumonitis was developed by only a few patients. In the case of modern breast radiotherapy, radiobiological modelling appears to be very sensitive to model and parameter selection giving clinically acceptable results in certain cases selectively (relative seriality model with Seppenwoolde et al and Gagliardi et al parameter sets). The use of published parameters should be considered as safe only after their examination using local clinical data. The variation of inter-patient radiosensitivity seems to play a significant role in the prediction of such low incidence rate complications. Scoring grades were combined to give stronger evidence of radiation pneumonitis since their differences could not be strictly associated with dose. This obviously reveals a weakness of the scoring related to this endpoint, and implies that the probability of radiation pneumonitis induction may be too low to be statistically analysed with high accuracy, at least with the latest advances of dose delivery in breast radiotherapy.     

Dosage compensation, the origin and the afterlife of sex chromosomes

Over the past 100 years Drosophila has been developed into an outstanding model system for the study of evolutionary processes. A fascinating aspect of evolution is the differentiation of sex chromosomes. Organisms with highly differentiated sex chromosomes, such as the mammalian X and Y, must compensate for the imbalance in gene dosage that this creates. The need to adjust the expression of sex-linked genes is a potent force driving the rise of regulatory mechanisms that act on an entire chromosome. This review will contrast the process of dosage compensation in Drosophila with the divergent strategies adopted by other model organisms. While the machinery of sex chromosome compensation is different in each instance, all share the ability to direct chromatin modifications to an entire chromosome. This review will also explore the idea that chromosome-targeting systems are sometimes adapted for other purposes. This appears the likely source of a chromosome-wide targeting system displayed by the Drosophila fourth chromosome.