Application of the European Test of Olfactory Capabilities in patients with olfactory impairment.

A central issue in olfaction concerns the characterization of loss of olfactory function: partial (hyposmia) or total (anosmia). This paper reports the application in a clinical setting of the European Test of Olfactory Capabilities (ETOC), combining odor detection and identification. The study included three phases. In phase 1, anosmics, hyposmics and controls were tested with the 16-items version of the ETOC. In phase 2, a short version of the ETOC was developed: patients with and controls without olfactory impairment were tested on a 6-items ETOC. In phase 3, to predict olfactory impairments in new individuals, the 16-items ETOC was administered on samples of young and older adults, and the 6-items version was applied in samples of young, elderly participants and Alzheimer patients. In phase 1, linear discriminant analysis (LDA) of ETOC scores classified patients and controls with 87.5 % accuracy. In phase 2, LDA provided 84 % correct classification. Results of phase 3 revealed: (1) 16-items ETOC: whereas in young adults, 10 % were classified as hyposmic and 90 % as normosmic, in elderly, 1 % were classified as anosmic, 39 % hyposmic and 60 % normosmic; (2) 6-items ETOC: 15 % of the young adults were classified as having olfactory impairment, compared to 28 % in the older group and 83 % in Alzheimer patients. In conclusion, the ETOC enables characterizing the prevalence of olfactory impairment in young subjects and in normal and pathological aging. Whereas the 16-items ETOC is more discriminant, the short ETOC may provide a fast (5-10 min) tool to assess olfaction in clinical settings.

Laryngeal graft after total laryngectomy in humans: A SWiM analysis.

Evaluation of the results of laryngeal transplantation (LT) in humans. Analysis of 3 bibliographic databases with the keywords "larynx, transplantation, autograft". In total, 626 abstracts were read and 25 articles selected. The main objective was to analyze the characteristics of laryngeal transplant patients. The accessory objectives comprised analysis of operative technique, immunosuppressive treatment and results. Four articles were selected for analysis. Two patients were transplanted after total laryngectomy for laryngeal carcinoma and 2 after laryngeal trauma. Three of the 4 patients had true transplantation with arterial, venous and neural microanastomosis. Two patients were decannulated and the tracheostomy tube was maintained in the other 2. Three of the 4 patients had good-quality phonation and could feed without a gastric tube. One patient died of carcinoma progression and 1 patient had to be explanted 14 years after transplantation. The number of LTs reported is too small for scientific determination of the place of this intervention in laryngology. The published results could, at first sight, suggest that the future of LT is uncertain. However, several elements, also suggest that otolaryngologists should continue to take an interest in this technique.

Thulium-YAG laser sialendoscopy for parotid and submandibular sialolithiasis.

OBJECTIVE: To evaluate the efficacy and safety of thulium-YAG laser in sialendoscopic fragmentation of salivary lithiasis. DESIGN: Retrospective, interventional case series. MATERIAL: Sixty-three patients treated by interventional sialendoscopy with thulium-Yag laser fragmentation between 2003 and 2010 at Edouard Herriot Hospital were included in the study. The laser was used for non-floating or large lithiasis (>4 mm). METHODS: The sialendoscopic thulium fiber laser was used in a pulsed mode with an average power output of 2-8 W to fragment and facilitate extraction of salivary stones. Several variables were studied: success rate, total number of procedures, total energy per procedure, size and number of salivary stones removed, and complications. RESULTS: Our series of 63 cases includes 40 cases of parotid lithiasis and 23 cases of submandibular lithiasis. In nine cases, two sessions of laser were performed. Stone size was evaluated pre-operatively by ultrasound and varied between 2 and 18 mm. Laser fragmentation was possible in every case. Complete extraction of the lithiasis was possible in 51 cases (73.9%) and partial extraction in eight cases (12.6%). Extraction failed in four cases (6.3%). Mean stone size was 5.4 mm (5.7 mm for parotid glands and 5.0 mm for sub-mandibular glands) and mean energy per procedure was 1,450 J (range: 1,400-1,800 J). Ductal perforations were observed in 12.7% of the cases. 65.1% of patients were free of symptoms with a mean follow-up of 18 months. CONCLUSION: Thulium-YAG laser appears to be an effective and safe technique in the treatment of salivary lithiasis.

[Learning curve in sialendoscopy: Our first 101 procedures]. / Courbe d'apprentissage en sialendoscopie : nos 101 premières procédures.

OBJECTIVE: To present our learning curve in diagnostic and interventional sialendoscopy for obstructive salivary diseases. MATERIALS AND METHODS: Monocentric descriptive retrospective study from March 2009 to July 2011. Clinical and demographic data were collected. We are particularly interested in arising technical issues, the use of combined approach, operative time, functional improvement as well as parameter changes over time. RESULTS: 92 operations were performed to explore 101 glands (63 parotid glands against 38 submandibular). We found 39.6% of stones and as many stenosis. The rate of complete stone removal was 65% and dilation was effective in 75% of stenosis. The median of the visual analog scale for pain was 1/10 and functional improvement was effective in 77%. The removal of the gland did not exceed 3.3%. No major complication was noted. Since the initiation of this activity, the median operative time was steady while procedures were more complex, with increased interventional sialendoscopy procedure often requiring combined approach. In about 25% of cases, we have been faced with technical issues. These have evolved over time: initially failure to enter the papilla, difficulty of removing large stones today. CONCLUSION: The learning curve in sialendoscopy allows rapid empowerment and acquisition of expertise in security. Mastery of this technique allows for innovative approaches, complementary to conventional procedure, without compromising neither the operative time nor the functional benefit.

Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming.

The initiation of T-cell-mediated antitumor immune responses requires the uptake and processing of tumor antigens by dendritic cells and their presentation on MHC-I molecules. Here we show in a human in vitro model system that exosomes, a population of small membrane vesicles secreted by living tumor cells, contain and transfer tumor antigens to dendritic cells. After mouse tumor exosome uptake, dendritic cells induce potent CD8+ T-cell-dependent antitumor effects on syngeneic and allogeneic established mouse tumors. Therefore, exosomes represent a novel source of tumor-rejection antigens for T-cell cross priming, relevant for immunointerventions.

A novel subset of human lymphocytes with a T cell receptor-gamma complex.

We have previously characterized a CD3+ T cell receptor (TCR) alpha/beta- human fetal cloned cell line, termed F6C7, which surface-expresses a CD3-associated gamma chain identified by anti-NKFi, an mAb with a restricted clonotypic reactivity. Here, we have produced an additional antibody, anti-Ti-gamma A, which recognizes a public epitope of the gamma molecule defined by anti-NKFi. Ti-gamma A is present on approximately 3% of circulating lymphocytes with a wide range (1-15%) among 30 healthy individuals tested. Two-color immunofluorescence experiments performed with anti-Ti-gamma A and BMA 031 mAb (a reagent specific for the TCR-alpha/beta receptor) showed that surface expression of Ti-alpha/beta and Ti-gamma A is mutually exclusive. Moreover, it was found that most Ti-gamma A+ cells are CD2+, CD3+, CD4-, CD5+, NKH1-, HLA class II-negative. In contrast, the expression of the CD8 molecule on these T lymphocytes appears to be variable from one individual to another. Finally, we found that Ti-gamma A+ cells represent a majority of peripheral lymphocytes that express CD3 proteins but not the TCR-alpha/beta heterodimer. The delineation of this unique lymphocyte subset should help further studies on the biology of cells with a CD3-associated gamma complex.

A unique V-J-C-rearranged gene encodes a gamma protein expressed on the majority of CD3+ T cell receptor-alpha/beta- circulating lymphocytes.

We have recently described an mAb, anti-Ti gamma A, that recognizes an antigenic determinant carried by a TCR gamma chain. This antibody binds to approximately 3% of human PBLs and delineates a CD2+, CD3+, TCR-alpha/beta-, CD4-, CD8+/-, CD5+, NKH1-, and HLA class II- subset. The present study was designed to identify the gene encoding the Ti gamma A epitope. A first analysis was carried out on a previously characterized TCR gamma + fetal-cloned cell line termed F6C7. It was found that F6C7 cells have one gamma rearrangement on each chromosome: one joins V gamma 3 to J gamma 1, and the second joins V gamma 9 to J gamma P. Because only the latter allele appeared to be transcribed in the F6C7 lymphocytes, these data strongly suggested that anti-Ti gamma A mAb is specific for either a V gamma 9 or a V gamma 9-J gamma P-encoded peptide. To confirm this point, we studied an additional series of 13 randomly selected Ti gamma A+ cloned cells derived from peripheral blood of three distinct adult individuals. Each one of these lymphocytes was shown to both possess and transcribe a V gamma 9-J gamma P-C gamma 1-rearranged gene. It is therefore concluded that a predominant subpopulation of CD3+ TCR-alpha/beta- human circulating T lymphocytes (namely, the subset defined by anti-Ti gamma A mAb) surface expresses a gamma protein with a limited potential of variability from one cell to another.

Further analysis of the T cell receptor gamma/delta+ peripheral lymphocyte subset. The V delta 1 gene segment is expressed with either C alpha or C delta.

In the present study, we have characterized the reactivity of two mAbs that are directed at the human TCR-gamma/delta. These reagents, designated anti-A13 and anti-TiV delta 2, were found to recognize antigenic determinants encoded by the TCR V delta 1 and V delta 2 gene segments, respectively. Immunofluorescence analyses performed with the antibodies confirmed that, in the TCR-gamma/delta+ cell subpopulation, the expression of V delta 2+ delta chains is largely predominant, as compared with the V delta 1+ counterparts. However, these experiments led to an apparently discrepant finding. Indeed, the total number of cells recognized by the anti-A13 plus the anti-TiV delta 2 antibodies was often greater than that detected with anti-TCR-delta 1, a reagent specific for a constant epitope of the human delta chain. Further investigation showed that the presence of a sizeable peripheral lymphocyte subset coexpressing the BMA031 and the A13 epitopes. Because the former antibody is known to recognize an invariant antigenic determinant of the TCR-alpha/beta dimer, these results suggested that the V delta 1 gene segment may be expressed with either C delta or C alpha. This hypothesis was confirmed using T2, an IL-2-dependent BMA031+ A13+ polyclonal cell line developed from peripheral blood of a healthy adult donor. Indeed, T2 cells were found to have productively rearranged the V delta 1 gene. Together, results of Northern blot analysis and cDNA cloning indicated that V delta 1 was expressed in these cells as part of a 1.6-kb full-length message including J alpha-C alpha segments.

Natural killer clones derived from fetal (25 wk) blood. Probing the human T cell receptor with WT31 monoclonal antibody.

We have conducted a phenotypic and functional analysis of 19 cloned cell lines generated after allogeneic stimulation of circulating lymphocytes from a normal human fetus aged 25 wk. Using a limited series of mAbs (Anti-T3, WT31, T4, T8, and NKH1A), cloned cells were found to fall in three groups. Three clones have a conventional "inducer" phenotype. Three clones have a phenotype (T3+, WT31+, T8+, and NKH1A+) similar to that of certain NK active mature T lymphocytes present in adult peripheral blood. In contrast, 13 cell lines display surface characteristics that have not been described previously. Indeed, they express T3 proteins but not the WT31 determinant. In light of previous studies, these results show that WT31 mAb is a unique reagent directed at an invariant epitope of the human T cell receptor that is not present on all circulating T3+ fetal lymphocytes. Functionally the T3+, WT31+, and NKH1A+ clones were found to kill immunizing LAZ 388 cells, as well as K562, while T3+, WT31- and NKH1A+ clones display NK-like function exclusively. Moreover, only WT31+ lymphocytes present in the cell line used for cloning experiments have the capacity to recognize alloantigen-bearing cells. Together, these data suggest that expression of WT31 may be necessary for recognition of alloantigens, while NK reactions mediated by T3+ lymphocytes are WT31-independent.

[Partial allotransplantation of the face including the mandible: a feasibility study]. / Allotransplantation partielle de face incluant l'os mandibulaire: étude de faisabilité.

OBJECTIVE: Facial grafts are useful in that they allow the repair of severe facial defects in one step in contrast to the actual available techniques which require staged procedures with limited cosmetic and functional results. The aim of our study was to determine whether it would be possible to include part of the mandible in a partial allotransplant of the face. MATERIAL AND METHODS: An anatomical study on the arterial and venous vascularisation of the face and the mandible was performed on 7 heads. Then nine heads were used to describe an anatomical model of harvesting two-thirds of the lower face. RESULTS: The study determined that a graft could be viable with a facial artery, inferior dental artery and two veins facial. Thus, a reliable method for harvesting hemi-mandible and total mandible is developed. The average sampling time was 4 hours and thirty minutes. Harvesting a total mandibular graft was more tedious because of the loss of joint laxity caused by the absence of mandibular osteotomy. CONCLUSION: Partial allotransplant of the face including the mandible is feasible. In such transplantations, functional difficulties related to the temporo-mandibular joint and orthognathic problems need to be overcome.

Sialendoscopy for sialolithiasis in children: 4-8 years follow up.

Sialolithiasis is rare in children, there are no guidelines for its treatment, and there are few, if any, long term follow-up studies. We report a retrospective review of medical records of children who were treated for sialolithiasis by sialendoscopy between 1 January 2007 and 31 December 2011, and who have been followed up for 4-8 years. Personal and clinical details, including age, sex, symptoms, whether the lithiasis was parotid or submandibular, the technique of sialendoscopy and complications, were recorded. Twenty-six children (30 sides) were successfully treated by sialendoscopy between 2007 and 2011 (mean (range) age 12 (3-17) years). Stones were removed from the parotid gland in four patients and the submandibular gland in 22. The main indication for sialendoscopy was swelling of the salivary gland during meals. Twenty-six procedures were done endoscopically. Twelve were treated with a wire basket alone, 10 by the combined approach, and laser was used in eight. Four patients developed complications, but without long-term effects. During follow-up of 4-8 years there were no recurrent swellings. We conclude that endoscopic treatment of stones in childhood is an efficient and conservative option for salivary glands, has few complications and no clinical recurrence at medium to long-term follow-up.

Imatinib enhances human melanoma cell susceptibility to TRAIL-induced cell death: Relationship to Bcl-2 family and caspase activation.

In order to define genetic determinants of primary and metastatic melanoma cell susceptibility to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we have applied oligonucleotide microarrays to TRAIL-sensitive primary T1 cells and TRAIL-resistant metastatic G1 cells treated or not with TRAIL. T1 and G1 cells are isogenic melanoma cell subclones. We examined 22 000 spots, 4.2% of which displayed differential expression in G1 and T1 cells. Cell susceptibility to TRAIL-mediated apoptosis was found to be correlated with gene expression signatures in this model. Some of the differentially expressed genes were identified as involved in ATP-binding and signaling pathways, based on previously published data. Further analysis provided evidences that c-kit was overexpressed in G1 cells while it was absent in T1 cells. The c-kit inhibitor, imatinib, did not restore TRAIL sensitivity, excluding a role for c-kit in TRAIL resistance in G1 cells. Surprisingly, imatinib inhibited cell proliferation and TRAIL-mediated apoptosis in melanoma cells. We investigated the possible involvement of several molecules, including c-ABL, platelet-derived growth factor receptor (PDGFR), cellular FADD-like interleukin-1 alpha-converting enzyme-like inhibitory protein (c-FLIP)(L/S), Fas-associated DD kinase, p53, p21(WAF1), proteins of B-cell leukemia/lymphoma 2 (Bcl-2) family and cytochrome c. Imatinib did not modulate the expression or activation of its own targets, such as c-ABL, PDGFRalpha and PDGFRbeta, but it did affect the expression of c-FLIP(L), BCL2-associated X protein (Bax) and Bcl-2. Moreover, c-FLIP(L) knockdown sensitized T1 cells to TRAIL-mediated apoptosis, with a sensitivity similar to that of cells previously treated with imatinib. More notably, we found that the resistance to TRAIL in G1 cells was correlated with constitutive c-FLIP(L) recruitment to the DISC and the inhibition of caspase 8, 3 and 9 processing. Moreover, c-FLIP(L) knockdown partly restored TRAIL sensitivity in G1 cells, indicating that the expression level of c-FLIP(L) and its interaction with TRAIL receptor2 play a crucial role in determining TRAIL resistance in metastatic melanoma cells. Our results also show that imatinib enhances TRAIL-induced cell death independently of BH3-interacting domain death agonist translocation, in a process involving the Bax:Bcl-X(L) ratio, Bax:Bcl-X(L)/Bcl-2 translocation, cytochrome c release and caspase activation. Our data indicate that imatinib sensitizes T1 cells by directly downregulating c-FLIP(L), with the use of an alternative pathway for antitumor activity, because PDGFRalpha is not activated in T1 cells and these cells do not express c-kit, c-ABL or PDGFRbeta. Caspase cascade activation and mitochondria also play a key role in the imatinib-mediated sensitization of melanoma cells to the proapoptotic action of TRAIL.

Three-dimensional modeling system for unilateral mandibular bone distraction: a clinical case.

Facial hemiatrophies are anomalies of the first branchial arch and affect one in 4000-5000 newborns. Bone distraction is the technique of choice for the treatment of these dysmorphoses. Mandibular osteodistraction requires prior determination of the characteristics of the distraction vector whose three components will serve to activate the distractor. The patient, aged 5 years, presented with a right facial hemiatrophy, Grade IB according to the classification of Pruzansky. Tomodensitometric acquisition was obtained with a CT scanner. Software specifically designed for this application allows segmentation of the anatomical elements by a region-growing algorithm. The 3D representation of each element is added to a 3D scene, in which are placed the built-up landmarks necessary for the surgical simulation after 3D cephalometric analysis. The surgical cleavage plane is oriented according to the surgeon's requirements while preserving the predominant anatomical elements. The software allows performance of rotations and translations of the bone segments rendered independently from the cleavage plane. The distances and angles covered during the virtual movement are measured at its conclusion. The aim of moving the bone segments is to render the mandibular occlusion plane parallel to the reference occlusion plane. The vertical growth of the maxilla is realized by secondary recuperation. The distractor used was of an external multidirectional type allowing elongation of the mandibular ramus and mandibular corpus, closure of the goniac angle, and lateralization or medialization of the ramus. On the 15th day, the mandibular angle was reduced by 10 degrees, which allowed closure of the anterior gap and recentering of the incisive areas by a half-cuspid. The patient presented with a complex bone deficit in the three spatial directions, which allowed the development of software for modeling the distraction. Other clinical cases will be necessary to validate this 3D imaging-based technique.

SOFA--an open source framework for medical simulation.

SOFA is a new open source framework primarily targeted at medical simulation research. Based on an advanced software architecture, it allows to (1) create complex and evolving simulations by combining new algorithms with algorithms already included in SOFA; (2) modify most parameters of the simulation--deformable behavior, surface representation, solver, constraints, collision algorithm, etc.--by simply editing an XML file; (3) build complex models from simpler ones using a scene-graph description; (4) efficiently simulate the dynamics of interacting objects using abstract equation solvers; and (5) reuse and easily compare a variety of available methods. In this paper we highlight the key concepts of the SOFA architecture and illustrate its potential through a series of examples.

[Labyrinthitis, or inflammatory pseudotumor after stapedectomy]. / Labyrinthite ou pseudotumeur inflammatoire après stapédectomie.

OBJECTIVES: To describe an extensive pseudotumor as a complication of stapes surgery. METHODS: Radiological workup and surgical exploration in a 38-year-old man suffering from postoperative hearing loss. The patient presented with tinnitus, inferior facial palsy, vertigo, and rapidly progressive hearing loss after his operation. RESULTS: The initial postoperative CT scan was normal. However, seven months after surgery, the CT scan showed an enlargement of the inner ear canal and complete vestibular destruction. The CISS sequence of the magnetic resonance imaging (MRI) enhanced after gadolinium injection revealed the presence of a mass filling the entire inner ear canal, the cochlear, the posterior labyrinth, and the middle ear. The aspect suggested an inflammatory pseudotumor. Surgical exploration confirmed the invasive aspect of the mass and pathological analysis revealed inflammatory tissue associated with microcalcifications. DISCUSSION: Hearing loss, vertigo, and tinnitus after stapes surgery require a radiologic workup. The CT scan is done first. It could be normal or eliminate other diagnoses. MRI may lead to a more precise diagnosis. It can reveal an inflammatory process of the inner ear after gadolinium injection. Surgical exploration is indicated in case of aggressive and extensive lesions. CONCLUSION: In the context of hearing loss complicating otosclerosis surgery, an imaging workup should include a CT scan. In case of a suspected expansive and inflammatory mass, it should be completed by an MRI (CISS sequence and gadolinium injection). An inflammatory lesion of the inner ear could indicate extensive pseudotumor.

Evidence for in situ amplification of cytotoxic T-lymphocytes with antitumor activity in a human regressive melanoma.

We have derived from lymphocytes infiltrating a human regressive melanoma lesion a series of T-cell receptor alpha/beta-dependent, HLA-B14-restricted cytotoxic T-lymphocyte clones reactive against the autologous tumor. Analysis of the T-cell receptor gene expression revealed that all the clones represented a unique cell expressing a V beta 13.1/J beta 1.1 gene segment. T-cell receptor transcripts expressed in the cloned cells were compared to those present in the uncultured tumor tissue. This analysis demonstrated that the specific cytotoxic T-lymphocyte clones characterized in vitro was actually selected and amplified in vivo at the lesion site. These results provide strong evidence that effector T-cells have contributed to tumor regression.

Tumor-specific immune response: current in vitro analyses may not reflect the in vivo immune status.

Although our knowledge and understanding of tumor-specific cytotoxic T lymphocytes (CTL) have expanded considerably, the long-term work needed to assay CTL has precluded their analysis in large numbers of patients. Moreover, in vitro culture steps may introduce major biases. New approaches to identify tumor-specific CTL clones would be helpful. As a means to describe the in situ immune status by T-cell repertoire analysis, we developed the Immunoscope approach, a PCR-based method that allows us to determine the spectra of CDR3 lengths of the TCR chains displayed by complex populations of T cells. We review here some of our data about melanoma. Tumor-infiltrating lymphocytes of a melanoma patient were analyzed by different means and melanoma-specific T-cell clones were derived. Two categories of tumor-specific CD8+ CTL clones were derived from the infiltrate of a tumor-proximal invaded lymph node. The majority of T-cell clones specifically lyse the autologous tumor cell lines and predominantly recognize the HLA-A2/MART-1(27-35) peptide complex. The in vivo representativity of such CTL was assessed by the immunoscope technology. Among three MART-1-specific clones, none was detectable in situ. The other kind of tumor-specific CD8+ CTL did not lyse autologous melanoma cell lines but lysed the "fresh" autologous tumor cells in a MHC class I dependent manner. The immunoscope approach revealed that one of the latter was detectable in situ among tumor-infiltrating lymphocytes although not among PBMC. These data indicate that melanoma-specific lymphocytes that could not have been selected through conventional screening procedures may be important in tumor rejection. Our results suggest that a better characterization of tumor-specific immune responses will be important for the optimization of specific immunotherapy strategies and the long-term follow-up of patients.

A layered model of a virtual human intestine for surgery simulation.

In this paper, we propose a new approach to simulate the small intestine in a context of laparoscopic surgery. The ultimate aim of this work is to simulate the training of a basic surgical gesture in real-time: moving aside the intestine to reach hidden areas of the abdomen. The main problem posed by this kind of simulation is animating the intestine. The problem comes from the nature of the intestine: a very long tube which is not isotropically elastic, and is contained in a volume that is small when compared to the intestine's length. It coils extensively and collides with itself in many places. To do this, we use a layered model to animate the intestine. The intestine's axis is animated as a linear mechanical component. A specific sphere-based model handles contacts and self-collisions. A skinning model is used to create the intestine's volume around the axis. This paper discusses and compares three different representations for skinning the intestine: a parametric surface model and two implicit surface models. The first implicit surface model uses point skeletons while the second uses local convolution surfaces. Using these models, we obtained good-looking results in real-time. Some videos of this work can be found in the online version at doi: 10.1016/j.media.2004.11.006 and at www-imagis.imag.fr/Publications/2004/FLAMCFC04.

Alternatively spliced T cell receptor transcripts expressed in human T lymphocytes.

We used the anchored-polymerase chain reaction (A-PCR) procedure to study human TCR transcripts derived from a variety of polyclonal T cell populations. In this series of experiments, 31 'unusual' cDNAs, which do not include exclusively V-J-C, J-C or 5'C genomic sequences, were identified. Ten of these were found to represent distinct types of alternatively spliced TCR alpha transcripts whose structure is derived from unusual splicing of one, two or even three intervening intronic sequences. The splicing events led to either conservation of a novel exon in the mRNA structure (designated aE1 alpha-aE5 alpha) between the V-J and C segments or to deletion of the 3' V region-J segment. In three cases, the alternatively spliced exons (aE1 alpha-aE3 alpha) interrupt the open translational reading frame of the corresponding V-J alpha segment. Nineteen and two cDNA represent sterile C beta or C delta transcripts, respectively. Their structures are derived from the conservation of a non-translatable exon, aE1 beta or aE1 delta, which is precisely spliced at the 5' end of the corresponding C exon sequences. Interestingly, the 3' region of the aE1 beta sequence is homologous to the murine C beta 0 exon. Together, these results led to the characterization of nine novel exons in the TCR alpha, beta and delta loci.