Increased entropy production in diaphragm muscle of PPAR alpha knockout mice.

Peroxisome proliferator activated receptor alpha (PPAR alpha) regulates fatty acid beta-oxidation (FAO) and plays a central role in the metabolic and energetic homeostasis of striated muscles. The thermodynamic consequences of the absence of PPAR alpha were investigated in diaphragm muscle of PPAR alpha knockout mice (KO). Statistical mechanics provides a powerful tool for determining entropy production, which quantifies irreversible chemical processes generated by myosin molecular motors and which is the product of thermodynamic force A/T (chemical affinity A and temperature T) and thermodynamic flow (myosin crossbridge (CB) cycle velocity upsilon). The behavior of both wild type (WT) and KO diaphragm was shown to be near-equilibrium and in a stationary state, but KO was farther from equilibrium than WT. In KO diaphragm, a substantial decrease in contractile function was associated with an increase in both A/T and upsilon and with profound histological injuries such as contraction band necrosis. There were no changes in PPAR delta and gamma expression levels or myosin heavy chain (MHC) patterns. In KO diaphragm, a marked increase in entropy production (A/T x upsilon) accounted for major thermodynamic dysfunction and a dramatic increase in irreversible chemical processes during the myosin CB cycle.

[Transitional carcinoma of the conjunctiva]. / Carcinome transitionnel de la conjonctive.

We report a case of transitional carcinoma originating from the conjunctiva. An 86-year-old woman was referred for a right conjunctival swelling lasting 6 months after a first surgical excision. The histopathological pattern revealed a transitional carcinoma, which usually originates from the airways and the lacrimal sac; recurrences are not uncommon. Transitional carcinoma may originate in the conjunctiva.

High-level expression, activation, and subcellular localization of p38-MAP kinase in thyroid neoplasms.

The p38 family of MAP kinases (p38-MAPKs) is involved in regulating the proliferation, survival, and migration of various cancer cells. The present study has investigated the expression, subcellular localization, phosphorylation, and activity of p38-MAPKs in normal and tumoural human thyroid tissues and in thyroid cell lines. The expression and nucleo-cytosolic compartmentalization of the alpha-isoform of p38-MAPKs (p38alpha-MAPK) were studied by western blotting in the WRO and B-CPAP cell lines, which are derived from human follicular and papillary thyroid carcinomas, respectively, and in the non-transformed rat thyroid cell lines FRTL-5 and PCCL3. Immunohistochemistry was used to study the expression and subcellular localization of p38alpha-MAPK, and of the phosphorylated forms of p38-MAPKs (P-p38-MAPKs) in human toxic adenomas (TAs), follicular adenomas (FAs), papillary thyroid carcinomas (PTCs), and follicular thyroid carcinomas (FTCs). The activity of p38-MAPKs in PTCs and FTCs was revealed by immunohistochemical detection of their typical phosphorylated substrate, MAPK-activated protein kinase 2/3 (MK2/3). p38alpha-MAPK was expressed in all cell lines and this expression was restricted to the cytosolic compartment. p38 MAPK activity was involved in regulating DNA synthesis in B-CPAP cells. p38alpha-MAPK and P-p38-MAPKs were strongly expressed in PTC and FTC cells, although only in the cytoplasm, whereas they were only very weakly expressed in FA cells, and absent in adjacent normal tissues. They were also expressed at a high level in TAs, but they were found in both nucleus and cytoplasm. Finally, phospho-MK2/3 immunostaining followed very similar patterns to those of p38alpha-MAPK and P-p38-MAPKs in PTCs and FTCs. Taken together, these results show for the first time that the p38-MAPK signalling cascade is functional in two types of differentiated carcinoma of the thyroid. The observation that p38-MAPK hyper-expression occurs in FTC, but not in FA, may provide an additional diagnostic tool for malignancy in some thyroid nodules.

Statistical mechanics of myosin molecular motors in skeletal muscles.

Statistical mechanics provides the link between microscopic properties of matter and its bulk properties. The grand canonical ensemble formalism was applied to contracting rat skeletal muscles, the soleus (SOL, n = 30) and the extensor digitalis longus (EDL, n = 30). Huxley's equations were used to calculate force (pi) per single crossbridge (CB), probabilities of six steps of the CB cycle, and peak muscle efficiency (Eff(max)). SOL and EDL were shown to be in near-equilibrium (CB cycle affinity 2.5 kJ/mol) and stationary state (linearity between CB cycle affinity and myosin ATPase rate). The molecular partition function (z) was higher in EDL (1.126+/-0.005) than in SOL (1.050+/-0.003). Both pi and Eff(max) were lower in EDL (8.3+/-0.1 pN and 38.1+/-0.2%, respectively) than in SOL (9.2+/-0.1 pN and 42.3+/-0.2%, respectively). The most populated step of the CB cycle was the last detached state (D3) (probability P(D3): 0.890+/-0.004 in EDL and 0.953+/-0.002 in SOL). In each muscle group, both pi and Eff(max) linearly decreased with z and statistical entropy and increased with P(D3). We concluded that statistical mechanics and Huxley's formalism provided a powerful combination for establishing an analytical link between chemomechanical properties of CBs, molecular partition function and statistical entropy.

Head and neck lesions in the immunocompromised host.

Head and neck lesions are encountered in more than 40-50% in patients with immunosuppression (HIV-infected individuals, diabetes mellitus, transplant recipients, patients treated with immunosuppressive drugs or post-radiotherapy). The organs affected are the salivary glands, the lymph nodes, the sinonasal tract, the orbits, the temporal bones, and the pharyngo-laryngeal mucosa. They are mainly involved by granulation tissue, perivascular and perineural inflammation, and neoplasms. In the pediatric population the temporal bone is the most frequent target organ. The most common clinical manifestation of salivary gland involvement is non-specific bilateral painless enlargement of the parotid gland and xerostomia. Lymphoepithelial cyst, sialosis, and lymphoma may be present. The high rate of salivary gland involvement is probably related to the presence of the human immunodeficiency virus within the saliva. Surgery, sclerotherapy by doxycycline, or low-dose radiotherapy may prevent further growth of tumoral lesions. Sinonasal diseases are the most frequent lesions which manifest in immunosuppressed adult patients (66%). They are associated with a trend of decreased survival rate. Invasive aspergillosis is defined by hyphae in the submucosa, and tumor necrosis without host inflammatory response; it may be lethal in 50-80%, especially when the skull base is involved. Computed tomography shows erosion of bone and extrasinonasal extension. The hypointensity of the lesion on T2-weighted images may suggest the diagnosis. Fungal sinus disease can affect 1-10% of transplant recipients and should be suspected when organ rejection is considered. The temporal bone is the most frequent target organ in the immunosuppressed pediatric population due to Eustachian,tube dysfunction. Otomastoïditis, necrotizing external otitis, and otosyphilis are reported. Prompt treatment may avoid lateral sinus thrombosis. Epithelial neoplasms, lymphomas, and Kaposi's sarcoma may also be considered. Kaposi's sarcoma, the most common neoplasm encountered in patients with AIDS, is an indicator of the progression of human immunodeficiency virus infection to AIDS. The lesions are often multifocal at presentation and may affect the skin, the mucosa, and visceral organs. The pathogenesis is unclear, but cytokines and growth factors may play a role. In conclusion, immunosuppressed patients are likely to develop virulent infection with vascular complications.

[Squamous cell carcinoma in a thyroglossal duct cyst]. / Carcinome épidermoïde sur kyste du tractus thyréogosse.

OBJECTIVE: To present a case of squamous cell carcinoma developed on a thyroglossal duct cyst in an adult patient. Modalities of treatment and prevention are discussed. PATIENT AND METHODS: A 55-year-old woman had a thyroglossal duct cyst since childhood. Surgical resection had not been performed because of parental refusal. RESULTS: Diagnosis of malignant degeneration was suggested by an increase in volume associated with cervical pain. Surgery was incomplete because of carotid artery and laryngeal involvement. Postoperative radiotherapy was given. At two years follow-up, local progression was controlled by palliative chemotherapy. DISCUSSION: For most authors, the risk of recurrent infections is the main reason for surgical resection of a thyroglossal duct cyst during childhood. The risk of malignant degeneration is generally not put forward. It is rather uncommon for carcinoma to develop on a thyroglossal duct cyst. The risk is probably underestimated because surgery is generally performed early in childhood. CONCLUSION: This observation of malignant degeneration emphasizes the importance of surgical resection of thyroglossal duct cysts during childhood. We discuss treatment in the event of malignant degeneration.

Chondromyxoid fibroma of the nasal bone with extension into the frontal and ethmoidal sinuses: report of one case and a review of the literature.

Chondromyxoid fibroma is a rare benign tumor that usually occurs in the long bones. A 50-year-old patient presented with chondromyxoid fibroma of the nasal bone with extension into the frontal and ethmoidal sinuses. This is the fourth case reported to date in the literature. The clinical manifestations of the tumor were very limited, and the appearance at rhinoscopy was misleading. Radiologic imaging showed a soft tissue lesion invading the adjacent bony structures and the dura mater. Surgery was performed by a combined team of otorhinolaryngologists and neurosurgeons, and total excision of the tumor was achieved. The histologic diagnosis of this tumor is difficult because of its similarities to chondrosarcoma. [Editorial comment: The authors concisely review management of this rare tumor, emphasizing that complete surgical excision, rather than curettage, is required for long term control.]

[Multicentric liposarcoma. Apropos of a case]. / Liposarcome multicentrique. A propos d'un cas.

INTRODUCTION: Though rare, observations of multiple liposarcomas show that the development of secondary tumors occur in sites usually considered as primary locations. This would be more frequent for myxoid liposarcomas than for other subtypes of the disease. Their origin, either multicentric (i.e., coexistence of several primary tumors) or due to metastatic spreading, is still debated. EXEGESIS: We report a case of myxoid-type multicentric (i.e., right popliteal fossa, retroperitoneum and soft tissue of the left arm) liposarcomas of different sizes, without pulmonary, hepatic or osseous involvement. These liposarcomas were simultaneously diagnosed in a patient who presented with pain in the right knee. CONCLUSION: This support the hypothesis that multiple liposarcomas have a multicentric origin. Initial and follow-up staging of such tumors must investigate not only usual metastatic sites but also classical primary locations.

[Unusual site of an embryonal rhabdomyosarcoma of the mesenchymal hepatic pedicle]. / Localisation inhabituelle d'un rhabdomyosarcome embryonnaire du mésenchyme pédiculaire hépatique.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of children. Tumors arising in the extrahepatic biliary tree are extremely rare (less than 1% of cases). In this location, most are RMS of the botryoid type. We report a case of a 10-year-old child with embryonal RMS arising in the mesenchyma of the hepatic pedicle. Most tumor cells were large, round with abundant eosinophilic cytoplasm. A few cells were small round or spindle-shaped. Tumor cells showed positive immunostaining for muscle markers: desmin and sarcomeric actin. Electron microscopy revealed 2 types of cells: some were undifferentiated and others showed striated muscle differentiation features.

[Pachydermoperiostosis with extramedullary hematopoiesis without myelofibrosis]. / Pachydermopériostose associée à un foyer d'hématopoïèse extra-médullaire sans myélofibrose.

BACKGROUND: In three previous reports of primary hypertrophic osteoarthropathy, an associated extramedullary hematopoiesis was related to myelofibrosis. CASE REPORT: A 44-year-old male patient with primary hypertrophic osteoarthropathy diagnosed when he was 34-year-old was referred to our hospital with an abdominal mass fortuitously detected. DISCUSSION: The present case is unique for the patient developed an extramedullary hematopoïesis without associated myelofibrosis. It suggests the possible intervention of growth factors common to the skin fibroblasts and the blood progenitor cells in the pathogenesis of primary osteoarthropathy.

Enhanced expression of interleukin-6 in bone and serum of metastatic renal cell carcinoma.

Interleukin-6 (IL-6) is produced by renal cell carcinoma (RCC) cell lines and primary tumors. Using immunohistochemical staining in two RCC patients with hypercalcemia and high serum levels of free and total IL-6, we showed expression of IL-6 in metastatic bone tissue. The role of IL-6 in hypercalcemia and bone resorption would suggest that bisphosphonates or dexamethasone could be useful as adjuvant therapy for IL-6 dependent bone metastases which fail to respond to interferon alpha (IFN) alpha 2a and all trans retinoic acid (ATRA).

Osteoid osteoma of the petrous bone.

We present a case of osteoid osteoma of the petrous bone presenting with progressive sensorineural hearing loss. CT showed a dense homogeneous mass at the promontory surrounded by a thin bony border. On MRI this lesion gave intermediate signal intensity on T1- and T2-weighted spin-echo images and enhanced intensely with gadolinium. Surgical removal and pathological study proved the diagnosis.

Correlation of granuloma structure with clinical outcome defines two types of idiopathic disseminated BCG infection.

Bacillus Calmette Guérin (BCG) is an attenuated strain of Mycobacterium bovis that is currently used as a live vaccine for human tuberculosis. Disseminated BCG infection may rarely occur following vaccination of children. In half of the cases, regarded as idiopathic, no well-defined immunodeficiency condition can account for the infection. However, the high rates of parental consanguinity and familial forms and the associated opportunistic infections with Salmonella suggest that these idiopathic BCG infections result from one or several new type(s) of inherited immune disorder(s). As an approach to the description and understanding of this newly described condition, the associated lesions were examined. Samples from 14 patients collected from a French national retrospective study were analysed. Pathological data from 22 cases reported in the world literature were also reviewed. Two types of granuloma were found. The first type (type I, tuberculoid) consisted of well-circumscribed and well-differentiated granulomas, with epithelioid and multinucleated giant cells containing very few acid-fast rods, surrounded by lymphocytes and fibrosis and occasionally with central caseous necrosis. The second type (type II, lepromatous-like) consisted of ill-defined and poorly differentiated granulomas, with few if any giant cells and lymphocytes but widespread macrophages loaded with acid-fast bacilli. Most children displayed a single type of granuloma. One half displayed type 1 lesions and the other half displayed type II lesions. There was a strong correlation between the type of granuloma and the clinical outcome. Tuberculoid lesions were associated with survival, whilst lepromatous-like lesions correlated with death. Correlation of granuloma structure with clinical outcome defines two types of idiopathic disseminated BCG infection. The phenotypic heterogeneity of the course of BCG infection reflects distinct pathogenic mechanisms and probably results from a genotypic heterogeneity of the underlying inherited immune disorder.

[Hemangioma of the facial nerve]. / Hémangiomes du nerf facial.

In this retrospective study the respective values of MRI and CT in the location and nature diagnoses of facial nerve haemangiomas were evaluated. The four male patients examined were 31, 44, 56 and 62 years old; they presented with facial nerve pals and/or cochlear-vestibular dysfunction. The haemangiomas were located in the internal auditory canal, the geniculate ganglion, the tympanic segment of the facial nerve and the petrous bone apex. MRI revealed a tumoral process, while CT showed intratumoral calcifications and provided a diagnosis of mass nature in two cases. In the other cases the pre-operative diagnosis was neurinoma of the VIIIth or VIIth cranial nerve. Histology ascertained the diagnosis. MRI is the method of choice in cases of facial paralysis or cochlear-vestibular dysfunction if a tumoral cause is suspected. Haemangioma is an uncommon tumour without specific image, except for calcifications and neighbouring osseous reactions. It must also be considered on the basis of clinical and topographical findings revealed by CT and MRI imaging.