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Biomedical subjects

M P Chenard

Publications and source records attributed to M P Chenard.

At least 19 recordsLinked to original sources

[Diffuse uptake of brown fat on computed-tomography coupled positron emission tomoscintigraphy (PET-CT) for the exploration of extra-adrenal pheochromocytoma].

We report an observation of strong bilateral uptake on a PET-CT scan compatible with activation of brown adipose tissue in a patient with extra-adrenal pheochromocytoma. A 42-year-old man was hospitalized for hypersudation together with weight loss and palpitations. Heart rate was 120 bpm and fasting blood glucose 1.36 g/l. Endocrine explorations revealed elevated serum chromogranine which reached 517 ng/ml (19-38). The norepinephrine level reached 49.7 nmol/l (<4.00) and urinary norepinephrine and normetanephrine levels reached 13977 nmol/24h (<414) and 32 micromol/24h (0.4-2.5) respectively. The thoraco-abdominal and pelvic scan showed a 6 cm diameter paraaortic hypervascularized mass with an infiltrative lesion of both perirenal area and mediastinal tissue without adenopathies. The abdominal MRI revealed the mass with a low intensity signal in T1 and a slight high intensity signal in T2. MIBG and octreoscan scintigraphies were negative. 18F-DG PET showed intensed uptake in the tumor mass together with intense, diffuse and bilateral uptake above and below the diaphragm. The mass was resected. Histological examination of the surgical specimen confirmed the diagnosis of extra-adrenal pheochromocytoma with an index of 13% cellular proliferation without cell atypia. There was a hypervascularization with small islets of brown adipose tissue in the perirenal fat. Both plasmatic and urinary catecholamines decreased to the normal range after the operation and PET-scan normalized. Bilateral spread of the radiotracer uptake was probably due to brown adipose tissue activation by excessive sympathetic stimulation induced by catecholamines released by the tumor.

Abdominal Neoplasms↗

Contribution of SISCOM imaging in the presurgical evaluation of temporal lobe epilepsy related to dysembryoplastic neuroepithelial tumors.

PURPOSE: Dysembryoplastic neuroepithelial tumors (DNTs) are a group of glioneuronal supratentorial and intracortical lesions often associated with the early onset of intractable and crippling partial seizures. They are characterized by their location, multinodular architecture, and heterogeneous cell composition, with a specific glioneuronal element in the specific form. Foci of cortical dysplasia may be associated with the tumoral lesion, and identifying the presence and the extent of cortical dysplasia is not always easy on magnetic resonance images (MRIs). The purpose of this article is to evaluate, retrospectively, the usefulness of ictal single-photon emission computed tomography (SPECT) imaging to assess the presence and the extent of cortical dysplasia associated with DNTs in nine patients with intractable temporal lobe epilepsy related to histopathologically confirmed DNTs. METHODS: The results of the subtraction of ictal and interictal SPECT coregistered to MRI (SISCOM) were compared with the results of the examinations of pathological material after surgery. RESULTS: SISCOM showed a strongly hyperperfused area corresponding anatomically to electroclinical abnormalities and to the location of DNTs on MRI. A circumscribed hyperperfusion was present in DNTs without cortical dysplasia, limited to the location of the tumor on MRI. In cases of associated cortical dysplasia, a widespread hyperperfusion including areas corresponding to normal perilesional regions on MRI was found. CONCLUSIONS: SISCOM, used among presurgical investigations, contributes to detecting cortical dysplasia associated with DNTs. Concordance between the symptomatogenic zone (defined from the medical history and electroclinical data), MRI scans, SISCOM pattern, and complete resection of the epileptic zone was predictive of a good postsurgical outcome.

Adolescent↗

High cancer cell death in syngeneic tumors developed in host mice deficient for the stromelysin-3 matrix metalloproteinase.

Matrix metalloproteinases (MMPs) are extracellular enzymes. Some of them are known to be involved in tumor development and/or progression. Several cellular functions have been proposed for MMPs during malignant processes. Notably, they may be involved in tissue-remodeling processes through their ability to digest matrix components or to participate in tumor neoangiogenesis and, subsequently, in cancer cell proliferation. One of these MMPs, stromelysin-3 (ST3/MMP11), although devoid of enzymatic activity against the matrix components, is associated with human tumor progression and poor patient clinical outcome. Using several in vivo experimental models, it has been demonstrated that ST3 expression by the fibroblastic cells surrounding malignant epithelial cells promotes tumorigenesis in a paracrine manner. The present study was devoted to the identification of the cellular function underlying this ST3-induced tumor promotion using a syngeneic tumorigenesis model in mice. Our results show that ST3 exhibits a new and unexpected role for a MMP, because ST3-increased tumorigenesis does not result from increased neoangiogenesis or cancer cell proliferation but from decreased cancer cell death through apoptosis and necrosis. Thus, during malignancy, the cellular function of ST3 is to favor cancer cell survival in the stromal environment.

Animals↗

An umbilical cord teratoma in a 17-week-old fetus.

A therapeutic abortion was conducted on a 17-week-old male fetus with a large umbilical cord teratoma associated with an exomphalos. A review of the literature revealed ten other cases of umbilical cord teratoma and shows that these tumors have a very polymorphic presentation. Four fetuses and infants died from various causes indicating that there is a need for close follow-up of pregnancies with umbilical cord teratoma.

Abortion, Therapeutic↗

A left pleural effusion with a calcified tumoral mass and left hemithoracic uptake on bone scan.

Diffuse malignant pleural mesothelioma is a rare primary tumor of the pleura with three principal histological types, epithelial; mesenchymal and mixed epithelial and mesenchymal. We report here a case of a mesenchymal mesothelioma with foci of osteosarcomatous degeneration revealed by dense calcifications associated with the pleural effusion on the computed tomography (CT) of the thorax. The bone scan revealed extraosseous uptake corresponding to the left pleura.

Aged↗

Analysis of allelic imbalance in patients with colorectal cancer according to stage and presence of synchronous liver metastases.

OBJECTIVE: To investigate the relationship between number and location of allelic imbalances (AI) and local tumor progression according to Astler-Coller classification. SUMMARY BACKGROUND DATA: Spontaneous errors in DNA replication (i.e., allelic imbalance or microsatellite instability) have been suggested to play an important role in carcinomatous transformation as reflecting alterations of gene function. METHODS: One hundred two consecutive patients with colorectal carcinoma undergoing surgical resection were included in this study. Patients were distributed according to the Astler-Coller classification as stages A (n = 7), B1 (n = 15), B2 (n = 24), C (n = 31), and D (n = 25). Fluorescent polymerase chain reaction was performed on frozen tumor, normal colon mucosa, and blood DNA at 35 microsatellite markers. Allelic imbalance frequency was compared with tumor staging. RESULTS: The percentage of AI was significantly higher in stage D than in A/B1 and B2. In addition, the percentage of AI was significantly higher in 10 synchronous colorectal liver metastases than in stage A/B1 and B2 tumors. However, the allelotyping revealed a subgroup of A/B1 tumors with a high AI frequency. Statistical analysis showed that the presence of AI at microsatellites D1S305, D2S138, D3S1282, D17S790, and D22S928 presented a significantly positive correlation with stages. CONCLUSION: The frequency of AI significantly correlates with tumor progression of colorectal cancer. Primary tumors with synchronous colorectal liver metastases showed a higher percentage of AI, suggesting that a frequency of AI greater than 35% with this selection of markers indicates a high risk of local progression and of development of metastases.

Adult↗

[Activity and cost analysis in surgical pathology. Experience of a French university laboratory using the activity-based costing method].

Good self-knowledge enables us to have a well- reasoned adaptation to our environment. Starting from this precept based on simple common sense, activity and cost analysis, when applied to medical departments in a university hospital setting, represents a necessary phase in their scientific progression and in the continuation of their university vocation. This is all the more true given the present climate of economic and organizational restructuring of medical facilities. This paper relates the experience of a French surgical pathology department which was assessed for cost effectiveness using the Activity-Based Costing (ABC) method in 1999. This method, which originated in the business world and of which the general concepts are presented here, has given us a keener understanding of the diverse processes involved, their costs and how these costs are arrived at. Moreover, this method has identified the proportion of costs imputable to diagnostic work and of those linked to work specific to a university hospital, in particular teaching and research and development. The results can then be used for a clearer analysis of the figures required by prescribers and health care funding agencies, and, within the department, to enhance perception of work carried out by the entire staff in order to initiate a new type of management centered on activity (Activity-Based Management). Adaptable to any medical department, whatever its organizational structure, independent of the significance of any given code letter and regardless of the rating method used to grade activities, the ABC method also allows for comparisons between structures of a similar nature. The thoughts it inspires on economic performance must take into account the rules of good medical practice, the imperatives of quality assurance, the need for "breathing space" which are indispensable to research and a humanist conception of working relations.

Costs and Cost Analysis↗

The steroidogenic acute regulatory protein homolog MLN64, a late endosomal cholesterol-binding protein.

MLN64 is a transmembrane protein that shares homology with the cholesterol binding domain (START domain) of the steroidogenic acute regulatory protein. The steroidogenic acute regulatory protein is located in the inner membrane of mitochondria, where it facilitates cholesterol import into the mitochondria. Crystallographic analysis showed that the START domain of MLN64 is a cholesterol-binding domain. The present work was undertaken to determine which step of the intracellular cholesterol pathway MLN64 participates in. Using immunocytofluorescence, MLN64 colocalizes with LBPA, a lipid found specifically in late endosomes. Electron microscopy indicates that MLN64 is restricted to the limiting membrane of late endosomes. Microinjection or endocytosis of specific antibodies shows that the START domain of MLN64 is cytoplasmic. Deletion and mutagenesis experiments demonstrate that the amino-terminal part of MLN64 is responsible for its addressing. Although this domain does not contain conventional dileucine- or tyrosine-based targeting signals, we show that a dileucine motif (Leu(66)-Leu(67)) and a tyrosine residue (Tyr(89)) are critical for the targeting or the proper folding of the molecule. Finally, MLN64 colocalizes with cholesterol and Niemann Pick C1 protein in late endosomes. However, complementation assays show that MLN64 is not involved in the Niemann Pick C2 disease which, results in cholesterol lysosomal accumulation. Together, our results show that MLN64 plays a role at the surface of the late endosomes, where it might shuttle cholesterol from the limiting membrane to cytoplasmic acceptor(s).

Animals↗

pS2/TFF1 interacts directly with the VWFC cysteine-rich domains of mucins.

BACKGROUND & AIMS: Trefoil factors (TFFs) are secreted gastrointestinal proteins that have been shown to protect and promote healing of the gastrointestinal tract. Moreover, pS2/TFF1 is essential for normal differentiation of the gastric mucosa because deficient mice develop antropyloric adenomas. To date, it is unclear how TFFs mediate their functions. METHODS: Using the yeast 2-hybrid system, we attempted to identify murine TFF1 interacting proteins by screening a stomach and duodenum complementary DNA (cDNA) expression library. RESULTS: Four positive clones were isolated. Sequence and expression studies showed that they corresponded to the murine counterpart of human cDNA sequences encoding carboxy-terminal fragments of mMuc2 (489 residues) and mMuc5AC (427, 430, and 894 residues) mucin proteins. Mutagenesis experiments showed that TFF1 interacts with the 2 mucins through binding with their VWFC1 and VWFC2 (von Willebrand factor C) cysteine-rich domains. CONCLUSIONS: These results show that the gastrointestinal protective effect of TFF1, and presumably of the other TFFs, is caused at least partially by their participation, via mucin binding, in the correct organization of the mucous layer that protects the apical side of the mucosa from deleterious luminal agents.

Amino Acid Sequence↗

Identification and characterization of a novel gastric peptide hormone: the motilin-related peptide.

BACKGROUND & AIMS: This study looked for new proteins with expression restricted to the gastric epithelium that may provide insight to the differentiation and function of the gastric unit. METHODS: A novel complementary DNA was isolated and sequenced, and its expression was examined in mouse tissues at both messenger RNA and protein levels. Subcellular localization was studied using immunoelectron microscopy. The posttraductional processing of the protein was analyzed in vitro by protein microsequencing and in vivo by Western blotting. RESULTS: We identified a novel protein that is mainly expressed by the secretory granules of the stomach enteroendocrine cells. This protein has sequence similarity with prepromotilin, the precursor of the motilin hormone and the motilin-associated peptide. As for the prepromotilin, a posttraductional maturation leads to a secreted peptide that is further cleaved at a dibasic site and gives rise to the motilin-related peptide (MTLRP) and MTLRP-associated peptide. CONCLUSIONS: We have identified and characterized a novel gene encoding the preproMTLRP protein. MTLRP presents similarity to motilin and is specifically expressed by enteroendocrine cells of the stomach and therefore represents a novel hormone.

Animals↗

[Large sections in routine breast pathology. A technique adapted to conservative surgery].

Large block macrosectioning of segmental excision specimens for breast cancer, and especially ductal carcinoma in situ, provides detailed information regarding size of the lesions, extent of spread and margin status which are essential for local recurrence risk assessment. However, the expansion of this technique has been curbed due to its reputation of being technically difficult, time-consuming, costly and providing slides of poor quality. We assessed the feasibility of the large section technique and adapted it to the everyday practice of a routine pathology laboratory. The time spent cutting a large block on a motorized microtome is half the time spent cutting the great number of conventional blocks needed to assess the same amount of tissue. Finally, 4 mm-thick stained large preparations of high quality are produced within 3 days after receiving the specimen. Analysis and report are both more precise and easier since the pathologist is saved the trouble of having to mentally re-assemble a great quantity of numbered small blocks. 805 primary monobloc segmental excision specimens have been examined in this way over the last 50 months period and we advocate its use as a standard procedure for breast-conserving surgery specimen management.

Breast Neoplasms↗

Presence of high levels of MT1-MMP protein in fibroblastic cells of human invasive carcinomas.

Matrix metalloproteinase 2 (MMP2) activity is associated with the aggressiveness of human cancers. Therefore, the mechanisms regulating its activation are of great interest for a better understanding of malignant invasive processes. MT1-MMP, a membrane-bound MMP, is involved in the conversion of the latent form of MMP2 to the active one. In the present study, we have raised 3 monoclonal antibodies (Mabs) directed against 3 different epitopes of human MT1-MMP, which we used to investigate the expression and cellular localization of MT1-MMP protein in human carcinomas. MT1-MMP protein was present in all invasive carcinomas tested, and it was almost exclusively located to the stromal cells and not to cancer cells as previously reported, suggesting that MMP2 activation might be a peri-fibroblastic event.

Animals↗

Hepatic and pulmonary metastases from a meningeal hemangiopericytoma and severe hypoglycemia due to abnormal secretion of insulin-like growth factor: a case report.

A 42-year-old woman was hospitalized for severe hypoglycemic coma. She had a voluminous hepatic metastasis and multiple small lung metastases from a meningeal hemangiopericytoma initially operated on 11 years earlier. High blood levels of an abnormal form of insulin-like growth factor type 2 (IGF II) associated with low blood levels of insulin, growth hormone, IGF I, and IGF BP3 were observed. After surgical resection of the liver and pulmonary metastases, serum glucose levels and hormonal abnormalities returned to normal.

Adult↗

Use of von Willebrand diseased kidney as donor in a pig-to-primate model of xenotransplantation.

BACKGROUND: The coagulation process in hyperacute and delayed xenograft rejection is essential and depends upon platelet adhesion and aggregation. The initial binding of platelets to the damaged endothelium is due to the interaction of the platelet receptor glycoprotein Ib with von Willebrand factor (vWF), which is present on activated endothelial cells and bound to the subendothelial matrix. We hypothesized that the use of organs from animals with homozygous von Willebrand disease (vWD), severely deficient in vWF, might prevent the thrombosis encountered in delayed xenograft rejection. METHODS: Ten baboons were treated by extracorporeal immunoadsorption of xenoreactive natural antibodies (XNA) through the donor pig liver to inhibit hyperacute rejection and received heterotopic vWD or control pig kidney xenografts. XNA levels, coagulation, and platelet activation markers were studied, and specimens of rejected kidneys were analyzed histologically. RESULTS: Although XNA depletion was comparable in both groups, neither kidney function nor survival times of control (n=5) or vWD (n=5) porcine kidneys showed any difference. Platelet and coagulation activation was evidenced in both groups after surgery and at rejection time. Immunohistochemical analysis revealed a weak endothelial vWF immunostaining in the rejected vWD kidneys, whereas it was undetectable in the nongrafted vWD kidneys, suggesting the deposition of baboon plasma vWF on the porcine vessels. CONCLUSIONS: The use of vWD organs did not improve the survival time of grafted kidneys in this xenotransplantation model. Further studies on the use of vWD organs, in association with other therapeutic approaches, such as complement inhibition, are nevertheless necessary to evaluate the usefulness of vWF deficiency as an adjunctive therapy to decrease the coagulation process during xenograft rejection.

Animals↗

Combined modality treatment for malignant transformation of a benign ovarian teratoma.

Malignant transformation of a mature teratoma is a rare event. Patients often remain free of symptoms until the tumor burden makes the prognosis poor, due to pelvic and peritoneal metastases. We present a case of squamous cell carcinoma arising from a teratoma, with bowel and peritoneal invasion. The patient was treated by radical surgery followed by whole pelvic radiation and chemotherapy. This regimen, usually given for squamous cell tumors, such as cervical cancer, led to a 19-month persistent disease-free survival.

Adult↗