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Active laser pyrometry and lock-in thermography were applied for non-destructive characterisation of a deposited carbon-layer (5–40 µm thickness, different thermal contact quality) on TEXTOR graphite tile. The experimental installation comprised a pulse repetition rate laser (Nd-YAG, 1064 nm, 0.5–250 ms pulse duration, 2 Hz to 1 kHz repetition rate, 10–100 W amplitude power) and a home-made active laser pyrometry system. Active laser pyrometry was used to obtain some unknown layer properties (thermal capacity, conductivity, optical absorptivity, layer/surface thermal contact coefficient). With the developed 3D theoretical model, it was possible to calculate the heated layer temperatures with a good temporal and spatial resolution. The layer characterisation was based on the comparison of the modelling and the measured temperatures. To complete active laser pyrometry, lock-in thermography measurements of the layer/surface thermal contact coefficient were made with a new model for rapid phase shifts calculations. The obtained coefficients in both methods were comparable. Though there was no gain in the measurements accuracy, lock-in thermography has demonstrated its advantage as being much more rapid for characterisation of deposited layers of micrometric thickness.

Lock-in thermography was applied to determine the thermal contact conductance of a W-layer (140 μm) on a CFC-substrate. A lock-in thermography system together with a pulse repetition rate Nd:YAG laser (1064 nm, 1–500 Hz pulse repetition rate) for layer heating was applied for phase shift measurements on the W-layer. A numerical model for direct phase shift calculations was developed and applied to rapid determination of the Fourier amplitudes and phases of the temperature. Thermal conductance coefficients were obtained by comparing the experimental and simulation phase shifts.

In modern fusion reactors, the erosion of plasma facing surface results in layers deposition on tokamak “cold” surfaces. To provide efficient operation of tokamaks, it is essential to characterise the deposited layer with high tritium content. In situ rapid surface characterisation without reactor components disassembly is required. Active laser pyrometry together with a repetition rate Nd–YAG laser (1 Hz–1 kHz repetition rate frequency) applied for surface heating can be used to characterise some thermo-physical properties (thermal capacity, thermal contact, and conductivity) of a micrometric layer. The pyrometer system was developed and applied to characterise some properties of a W-layer (140 μm) on a CFC-substrate. The numerical code developed for 3-D simulation of LH of a surface with the deposited layer was applied to simulate the experimental heating temperatures. The experimental and simulation results were compared. W-layer characterisation was performed by fitting the experimental and theoretical heating temperatures.

Cherenkov measurements can be advantageously carried out using a counting instrumentation dedicated to liquid scintillation. In the case of radionuclide measurements, the interest of this technique is largely described in the literature. For instance, it is generally quoted that the possibility to measure directly the activity of aqueous solutions makes the sample preparation easier. Based on a three-photomultipliers apparatus, the Triple to Double Coincidence Ratio (TDCR) method is implemented in National Metrology Institutes for liquid scintillation measurements. Knowing the decay scheme associated with the radionuclide to be standardized, a free parameter model of light emission is constructed to determine the counter detection efficiency using the experimental TDCR value. Contrary to liquid scintillation, Cherenkov emission is characterized by a directional behavior. Instead of using an additional free parameter to take this effect into account, a stochastic modeling based on the Monte Carlo code Geant4 is proposed in order to extend the TDCR method to Cherenkov counting. The purpose of this model is to simulate the different optical processes of Cherenkov photons leading to the production of photoelectrons in the three-photomultipliers counter. The validation of this stochastic approach of the TDCR method for Cherenkov counting is carried out in the case of 90Y activity measurements.

The half-life of 233U was determined by a specific activity method, in the frame of an international collaboration project of four metrology institutes. A purified, highly enriched 233U solution was prepared with certified concentration of uranium isotopes. The isotopic composition of the uranium material was determined by thermal ionization mass spectrometry. The ingrowth of daughter nuclides was calculated and confirmed by ?-particle and ?-ray spectrometry measurements. Quantitative sources were prepared from aliquots of the 233U solution and their disintegration rate was determined by means of ?-particle counting at a defined small solid angle, liquid-scintillation counting and 4? counting in a pressurized proportional counter and in a CsI(Tl) sandwich spectrometer. A half-life value of 1.5867 (14) ? 105 a was obtained, in which the relative standard uncertainty amounts to 0.09%. The result is lower than the currently recommended value of 1.592 (2) ? 105 a and a new best estimate of T1/2(233U) = 1.5903 (13) ? 105 a was calculated from a partially weighted mean of a set of published data.

Focal forms of congenital hyperinsulinism are due to a constitutional heterozygous mutation of paternal origin in the ABCC8 gene, more often than the KCNJ11 gene, located in the 11p15.1 region. This mutation is associated with the loss of the maternally inherited 11p15.1 to 11p15.5 region in the lesion. We investigated the possible occurrence of a compensatory duplication of the paternal 11p15.1-11p15.5 region.A combined immunohistochemistry and fluorescent in situ hybridization study on beta-cell interphase nuclei with probes covering two genes located in this region (ABCC8 and CDKN1C genes) was performed in four cases of focal forms of hyperinsulinism.beta-Cells in the lesions of four cases of focal congenital hyperinsulinism were diploid for chromosomes 11 and 13. The 11p15.1 to 11p15.2 and 11p15.4 to 11p15.5 regions containing ABCC8 and CDKN1C genes, respectively, were present with two copies. Loss of the maternal allele was confirmed in these focal lesions with microsatellite markers flanking the ABCC8 and CDKN1C genes, whereas a heterozygous mutation in the ABCC8 gene was inherited from the father.There is a duplication of the paternal allele on chromosome 11 in the focal forms of hyperinsulinism lesion. The paternal isodisomy observed rendered the beta-cells homozygous for ABCC8 mutation and harbored a K-channel defect in the lesion similar to that observed in diffuse forms of congenital hyperinsulinism.

Rhenium-186 has several current and potential applications in nuclear medicine. It decays by beta minus emissions mainly to the fundamental and the 137 keV excited levels of 186 Os and by electron capture to 186 W. This paper describes the standardization of this radionuclide using the Triple to Double Coincidence Ratio model (TDCR) method. This is done by the calculation of the energy transferred to the scintillator by considering the various decay/de-excitation paths following the disintegration of the nuclide. The uncertainty on the detection efficiency is evaluated by stochastic methods by considering statistical distribution of theoretical and experimental parameters used in the calculation model. The detection efficiency was found to be higher than 97%, allowing a relative standard uncertainty on the activity determination of about 0.3%.

Resume Chez l’enfant, la sarcoidose est rare et peut revetir des aspects trompeurs. Les auteurs rapportent l’observation d’un enfant âge de 13 ans explore pour une fievre prolongee, un syndrome inflammatoire et des lesions cutanees. L’echographie abdominale a montre une hepatomegalie, des adenopathies mesenteriques et un nodule splenique. Le scanner thoracique a visualise des adenopathies hilaires bilaterales. La biopsie d’une adenopathie inguinale a conclu a une tuberculose caseofolliculaire. L’echec du traitement antituberculeux, la fievre elevee, la negativite de l’intradermoreaction a la tuberculine et les resultats de la biopsie cutanee ont fait suspecter le diagnostic de sarcoidose. Celui-ci a ete conforte par les resultats du lavage broncho-alveolaire, le taux eleve de l’enzyme de conversion de l’angiotensine et le controle de l’examen anatomopathologique. L’evolution sous corticotherapie a forte dose a ete favorable. La sarcoidose, meme si elle est rare chez l’enfant, doit etre evoquee devant une fievre prolongee et un syndrome inflammatoire important.

BACKGROUND In prostate cancer cell lines, androgen receptor (AR) coactivators modulate the transcriptional activity of AR. However, very little is known about their expression in normal prostate tissue and during progression to cancer. METHODS AR and coactivators ARA54, ARA55, ARA70, and SRC1 RNA were analyzed by RT-PCR in normal and tumoral tissues of the same prostate, in prostate cell lines, and after hormonal treatments of prostate epithelial cells. RESULTS AR-coactivators were expressed in normal and tumoral tissues and in cultured prostate cells; only ARA55 expression was decreased in tumoral relative to normal tissue of all seven prostates analyzed. It was not expressed in LNCaP and DU145 cancer cells and low in PNT2 immortalized cells in which all coactivator's expression were down regulated by DHT and up regulated by E2. In addition, coactivator's expression was increased in hyperplastic relative to normal prostate fibroblasts. CONCLUSIONS ARA55 is both an AR coactivator and a focal adhesion protein (Hic-5). Its role in the progression of prostate carcinoma may therefore involve these two different functions. Its decrease in cancer tissue suggests that it plays a different role than that expected, namely, facilitate cell proliferation and therefore mobility and metastasis. Prostate 56: 192–200, 2003. © 2003 Wiley-Liss, Inc.

A locus on distal 9p has been reported to be deleted in patients with mental retardation, craniofacial dysmorphic traits, notably trigonocephaly, and a high frequency of genital and/or gonadal anomalies (Alfi's syndrome).1 More recently, some cases of 46,XY male to female sex reversal without dysmorphic traits have been described in association with distal deletions of 9p.2–5 46,XY patients described so far have had gonadal anomalies ranging from streak gonads, to partially masculinised dysgenetic gonads, to normal testes. A family of genes containing a unique zinc finger DNA binding domain, which has been called DM, as it is contained in two proteins involved in invertebrate sex determination, doublesex and mab-3, has recently been recognised. Three genes belonging to this family have been identified on 9p24.3, immediately proximal to the centromeric boundary of the minimal region, which is required in two copies for testis development.5 The first gene identified was termed DMRT1 and the two additional DM gene family members are placed in tandem more distally to the breakpoint of the minimal deleted region.6,7 DMRT1 is transcribed only in the embryonic gonads of both sexes and in fetal and adult testis, and is required for postnatal differentiation of both somatic and germ cells in the mouse testis.8 Therefore, this gene is a good candidate to explain the 46,XY sex reversal associated with 9p deletions. Recently, a 1 year old 46,XX female patient with premature ovarian failure and deletion of 9p was reported.9 This led to the suggestion of a role for a gene located on 9p in both male and female gonadal development. DMRT1 represents a good candidate for a function in both sexes as it is expressed in the genital ridge in both sexes in mouse and humans.7,8 Here, we report …

Aims We report a case study to highlight the occurrence of glioblastoma multiforme in an ovarian teratoma. Methods and results A 10-year-old girl presented with a left frontal lobe primitive neuroectodermal tumour which was successfully treated. After 6 uneventful years, she developed glioblastoma multiforme located posterior to the site of the initial tumour. Six years later, she presented with a mature cystic teratoma containing glioblastoma multiforme. Conclusions Glioblastoma in an ovarian teratoma is an exceptional event, which might have an initial clinical presentation as a metastatic brain tumour. Alternatively, recurring glial tumours may occur in a genetically predisposed person; the role of radiation and chemotherapy in this context remains to be elucidated.

The aim of this study was to report the presentation and outcome of 22 consecutive children (13 female) who presented with a syndrome of chronic intestinal pseudo-obstruction with or without urinary tract involvement. We analyse the main clinical and histopathological features and discuss therapeutic management. Ten patients had signs of intestinal obstruction at birth, in which 6 presented antenatally with megacystis on ultrasound. Six children presented with constipation and/or obstruction between 1 and 6 months of age and in 6 other patients diagnosis was made between the ages of 1 and 12 years. There was a family history in 4 patients. Investigations showed diffusely dilated gut on x-ray with slow transit on small bowel follow through. Absent or abnormal motor migrating complex with low amplitude contractions were demonstrated on duodeno-jejunal manometry in 12/13. Megacystis occurred in 15/21 and megaureter in 2/21. Full thickness biopsies (n = 22) revealed involvement of muscle layers in 8, and abnormal myenteric plexus on histochemistry in 13. In 1, the biopsies were inconclusive. Recurrent urinary tract infections occurred in all with structural urinary tract abnormality and most had bacterial overgrowth. Severe recurrent episodes of obstruction which required parenteral nutrition (PN) occurred in all patients. Drugs were unhelpful and decompression ileostomies or colostomies were performed in 20/22. Five children died from sepsis (n = 3) or sudden death. Eleven patients remain partially or totally dependent on PN despite decompression ileostomy in 10/11. Six patients underwent colectomy and ileorectal pull-through, 2 of which remain on long-term PN, while the others are totally orally fed. Despite careful histological study pointing to 2 main forms, myopathy and neuropathy, the etiology of primary intestinal pseudoobstruction syndromes remains unknown. It may present antenatally while most of the time the gut and the urinary tract are diffusely involved. The condition has a high morbidity with a percentage requiring long-term PN. Although the mortality rate is high (23%), careful treatment of urinary tract infections and bacterial overgrowth, decompression surgery and judicious use of PN allows survival to adult life.

Resume L'exploration fonctionnelle nasale est encore peu utilisee en France chez l'enfant asthmatique et chez l'enfant souffrant de rhinites non infectieuses durables et resistantes aux traitements. L'utilisation de scores cliniques, la mesure de l'obstruction par rhinomanometrie, la recherche de l'eosinophilie sur des secretions nasales correctement recueillies, permettent une meilleure approche du diagnostic et du traitement de ces rhinites dont la frequence et le retentissement socio-economique augmentent regulierement dans les pays industrialises.

The intracellular parasite Listeria monocytogenes is able to induce its internalization by cultured mammalian cells that are not normally phagocytic. This process requires the expression of the chromosomal locus inlAB. We studied the virulence of an inlAB mutant and of its parent in murine listeriosis. Irrespective of the route of inoculation, the inlAB mutant was severely attenuated for growth in the liver. The livers of mice inoculated with the inlAB mutant displayed much smaller infectious foci than the parent as early as 24 h after infection. Electron microscopy showed that these foci consisted of a few inflammatory cells, with few bacteria; bacteria were rarely found within hepatocytes. In contrast, foci in livers of mice inoculated with the parent consisted of islets of heavily infected hepatocytes that were infiltrated by numerous neutrophils; bacteria seemed intact within hepatocytes and damaged within neutrophils. A direct role of inlAB for the entry of L. monocytogenes into hepatocytes was confirmed in a cell infection system using the murine embryonic hepatocyte cell line TIB73. The inlAB mutant was approximately 20-fold less invasive in trans. The "invasion locus" inlAB contributes to protect L. monocytogenes from the host's innate defense mechanisms by promoting its entry into hepatocytes.

OBJECTIVE Testicular differentiation can occur in the absence of the Y chromosome giving XX sex-reversed males. Although Y chromosomal sequences can be detected in the majority of male subjects with a 46,XX karyotype, several studies have shown that approximately 10% of patients lack Y material including the SRY gene. The aim of this study was to see if the classification of XX sex-reversed individuals into three groups, Y-DNA-positive phenotypically normal XX males, Y-DNA-negative XX males with genital ambiguities and Y-DNA-negative true hermaphrodites can be applied to our cases. DESIGN Endocrinological and genetic studies were conducted in 20 XX sex-reversed patients. PATIENTS Twenty patients with various phenotypes were studied. They were between 20 days and 35 years old. Ten presented ambiguous external genitalia (Prader's stages II to IV). After laparotomy or gonadal biopsy, the diagnosis was 46,XX true hermaphroditism in five, and XX male in 15. MEASUREMENTS Blood samples were obtained from all patients for hormonal and molecular studies. Basal levels of testosterone, oestradiol and pituitary gonadotrophins were measured by RIA. In addition, two stimulation tests were performed: gonadotrophin stimulation with GnRH and testicular stimulation with hCG. Several Y-specific DNA sequences of the short arm of the Y chromosome were analysed by Southern blot and polymerase chain reaction methods. RESULTS In this study, three categories of XX sex-reversed individuals were observed: phenotypically normal males with or without gynaecomastia, males with genital ambiguities, and true hermaphrodites. Endocrinological data were similar in XX males and in true hermaphrodites. Testosterone levels exhibited normal (n = 9) or decreased (n = 11) values. The hCG response was low. FSH and LH were elevated in 13 patients. Molecular analysis in ten patients showed varying amounts of Y material including the Y boundary and SRY. Ten patients with various phenotypes lacked Y chromosomal DNA. There was no relation between Leydig cell function (as indicated by testosterone levels before or after hCG stimulation) and the presence of Y chromosome material. CONCLUSION Although the presence of Y-specific DNA generally results in a more masculinized phenotype, exceptions do occur. In the Y-DNA-negative group, complete or incomplete masculinization in the absence of SRY suggests a mutation of one or more downstream non-Y, testis-determining genes.

The Foxl-2 gene is involved in eyelid and ovary development. Mutations can lead to a shortened protein and malformations such as BPES associated or not to POF. Forkhead point mutation C134W is a marker of adult type granulosa cell tumors only. Foxl-2 dysregulation is also present in DSD and DSD associated tumors such as Gonadoblastoma and gonadoblastoma like intratubular undetermined germ cell neoplasia. A similar spectrum of pathology involvement is also found for WT1 and RET and gives a new insight into the relationship between development, malformations and oncogenesis.

An international Key Comparison of (177)Lu has recently been carried out. Twelve laboratories performed assays for radioactivity content on aliquots of a common master solution of (177)Lu, leading to eleven results submitted for entry into the Key Comparison Database of the Mutual Recognition Arrangement. A proposed Comparison Reference Value (CRV) was calculated to be 3.288(4)MBq/g using all eleven results. Degrees of equivalence and their uncertainties were calculated for each laboratory based on the CRV. Most of the values reported by the participating laboratories were within 0.6% of the CRV.

Infants with congenital diaphragmatic hernia (CDH) die, because their lungs are hypoplastic and their pulmonary vascular resistance remains elevated after birth. In human newborns, it is difficult to appreciate the benefit of new therapeutic approaches, because the pathological findings are not uniform, the disease is rare and the clinical criteria for poor prognosis with conventional therapy are uncertain. To study the benefit of high-frequency ventilation (HFV) the use of Tolazoline in CDH, we created a diaphragmatic defect in sheep fetuses at 0.6 gestation and studied full-term newborns after a caesarian section. A sternotomy was performed to place catheters and flow probes on the aorta and pulmonary artery and to clamp the ductus arteriosus and the left pulmonary artery. Twins were used as control, and the CDH lambs were either ventilated with conventional ventilation (CV) or HFV. 23 ewes were operated upon with a 22% abortion rate and 31 newborn lambs (10 controls and 21 CDH) were studied. A complete gasometric and hemodynamic study was performed in 23 lambs (7 controls, 8 CDH with CV and 8 CDH with HFV). Clinical and pathological findings of the lambs with CDH were very similar to severe CDH in humans with bilateral lung hypoplasia, severe respiratory distress, high pulmonary vascular resistance and severe hypoxemia. HFV dramatically improved CO2 elimination, allowed less aggressive ventilation, and was associated with higher flows and lower systemic and pulmonary vascular resistance. However, HFV did not improve oxygenation leaving the newborn with severe hypoxemia associated with massive intrapulmonary foramen ovale shunting from right to left.

Chronic intestinal pseudo-obstruction (CIPO) is a severe disease of the digestive tract motility. In pediatric population, CIPO remains of unknown origin for most patients. Chronic intestinal pseudo-obstruction is also a common feature in the course of mitochondrial oxidative phosphorylation disorders related for some patients to mutations in TYMP, POLG1, mtDNA tRNA(leu(UUR)) or tRNA(lys) genes. We hypothesized that CIPOs could be the presenting symptom of respiratory chain enzyme deficiency and thus we investigated oxidative phosphorylation in small bowel and/or colon smooth muscle of primary CIPO children.We studied eight children with CIPO and 12 pediatric controls. We collected clinical, radiological and pathological data and measured respiratory chain enzymatic activity in isolated smooth muscle of the small bowel and/or the colon. We also sequenced TYMP, POLG, mtDNA tRNA(leu(UUR)) and tRNA(lys) genes.Neither pathological nor radiological data were in favor of a mitochondrial dysfunction. No respiratory chain enzyme deficiency was detected in CIPO children. In myogenic CIPO, respiratory enzymes and citrate synthase activities were increased in small bowel and/or colon whereas no abnormality was noted in neurogenic and unclassified CIPO. Levels of enzyme activities were higher in control small bowel than in control colon muscle. Sequencing of TYMP, POLG, mtDNA tRNA(leu(UUR)) and tRNA(lys) genes and POLG gene did not reveal mutation for any of the patients.The normal enzymatic activities as the lack of radiological and genetic abnormalities indicate that, at variance with adult patients, oxidative phosphorylation deficiency is not a common cause of childhood CIPO.

Determine high-resolution tomography (HRCT) scan characteristics in children with SFTPC mutation and correlate them to histological findings.This retrospective multicenter study included 15 children (7 females and 8 males) with SFTPC mutations. HRCT scans have been performed in all the children and lung biopsies in 8 children.From all signs assessed on initial HRCT scans, ground-glass opacities (n =14, 93%) and lung cysts (n = 6, 40%) were predominant. Interlobular septal thickening (n = 1, 7%), air space consolidation (n = 1, 7%), paraseptal emphysema (n = 2, 13%), and pulmonary nodules (n = 1, 7%) were also found. Histological analysis revealed accumulation of macrophages in the alveolar lumen, type II pneumocyte hyperplasia, and alveolar septal thickening. Dilatation of the respiratory bronchiole and alveolar duct associated with muscular hyperplasia were also described. Interestingly, lung cysts on HRCT scans were associated with dilatation of terminal bronchioli and alveolar duct in lung biopsies.In children with SFTPC mutations, HRCT scan finding was highly correlated to the histological findings and, as such, represent a useful tool to identify patients that may require SFTPC gene sequencing.

The principle of the Compton source efficiency tracing method (CET) in liquid scintillation counting (LSC) is to use, as a tracer, a Compton electron source temporarily created inside the source being measured. The tracer source and the source to measure have thus exactly the same chemical composition. A main advantage anticipated for this measurement method is its low sensitivity to the kB factor and insensitivity to the chemical composition and quenching of the source, which would obviate the necessity to develop a reference liquid scintillator cocktail in the framework of an international reference system for the measurement of pure-beta emitters by LSC. We took the opportunity of a tritiated water international activity measurement in comparison to prepare LS sources using various commercial liquid scintillator cocktails. Tritium is assumed to be a good candidate for testing the LSC activity measurement method, as the detection efficiency is rather low and the effect of the ionization quenching parameter, kB, on the detection efficiency calculation by the TDCR method is known to be important. The sources were measured using a TDCR counter equipped with a Compton spectrometer in order to apply the CET method. The measurements are analyzed using both the TDCR method and CET method in order to deduce the optimal calculation parameters. The detection efficiency range covered by these experiments is from 0.4 to 0.6, allowing a good test of the validity of the physical assumptions included in the calculation model. The paper will conclude on the advantages and drawbacks of using this CET method in the framework of an international reference system for low-energy pure-beta radionuclides.

Liquid scintillation counting (LSC) is widely used at LNHB for primary standardization of radionuclides (TDCR method), for secondary calibration and also for source stability studies or radioactive purity measurements. A total of five LSC counters are used for these purposes: two locally developed 3-photodetector counters for the implementation of the TDCR method, two Wallac 1414 counters and one Wallac 1220 Quantulus counter. The quality of the LSC measurements relies on the correct operation of these counters and their traceability to the frequency and time units.

The aims of our paper were to establish the main histopathological, histochemical and immunohistochemical aspects of tumoral stroma from salivary pleomorphic adenomas. For this purpose we investigated 103 cases by the classical histopathological technique with paraffin embedding and staining with Hematoxylin-Eosin (HE), Hematoxylin-Eosin-Safranin (HES), trichromic Masson, trichromic Goldner Szeckelly, orcein and Periodic Acid Schiff-Blue Alcian (PAS-AA). Immunohistochemically, they were investigated for AE1-AE3, MNF116, CK8, EMA, vimentin, alpha-actin calponin, S-100, GFAP, collagen IV, and PCNA. The results of our study suggest the key role of neoplastic myoepithelial cell in the achievement of diverse morphological aspects of stroma in such neoplasms.

Hermaphroditism is a more general term for the discrepancy between the phenotype and the genotype of sex development than sexual ambiguity, which refers mainly to external genitalia anomalies. Hermaphroditism is studied on an historical and pathogenetical perspective. Short embryological summaries are integrated. The defects of sexual differentiation due to a hormonal deficiency are first studied: androgen insensitivity, steroid 5 alpha-reductase 2 deficiency, defects of testosterone synthesis, persistent mullerian ducts syndrome. Sexual determinism deficiencies come after: Turner syndrome, XX males, pure gonadal dysgenesis, and true hermaphroditism, mixed gonadal dysgenesis, Drash and Frasier syndrome. Tumors of dysgenetic gonads followed. Mixed tumors developed in dysgenetic gonads are gonadoblastoma and dysgerminoma. Sex cord tumors are androgen insensitivity associated tumors, Leydig cells tumors and adrenal cell inclusion tumors. New perspectives open by sex reversion genes are open.

Congenital hyperinsulinism (HI) is the most important cause of hypoglycaemia in early infancy. The inappropriate oversecretion of insulin is responsible for profound hypoglycaemias requiring aggressive treatment to prevent severe and irreversible brain damage. Several classifications of HI can be attempted, based on: 1) the onset of hypoglycemia in the neonatal period or later in infancy; 2) the histological lesion: focal or diffuse; 3) the genetic transmission: sporadic, recessive, or less frequently dominant. The most common underlying mechanism of HI is dysfunction of the pancreatic ATP-sensitive potassium channel (K(+)(ATP)). The 2 subunits of the K(+)(ATP) channel are encoded by either the sulfonylurea receptor gene (SUR1 or ABCC8) or the inward-rectifying potassium channel gene (KIR6.2. or KCNJ11), both located in the 11p15.1 region. Focal CHI has been shown to result from a paternally inherited mutation on the SUR1 or KIR6.2 gene and loss of the maternal 11p15 allele restricted to the pancreatic lesion. Diffuse HI, frequently due to mutations of the SUR1 or KIR6.2 genes of autosomal recessive inheritance is genetically heterogeneous. The distinction between the focal and the diffuse HI is very important, because the treatments are different. To distinguish between focal and diffuse HI, transhepatic catheterisation with pancreatic venous sampling was the reference technique, but will likely be replaced by [(18)F] Fluoro-L-Dopa PET scan, which is easier to perform. In absence of response to the medical treatment (diazoxide) a limited pancreatectomy permits to cure focal HI, while a diffuse HI requires a subtotal pancreatectomy with high risk of subsequent diabetes mellitus.

The purpose of this study has been to establish the major ultrastructural aspects of the myoepithelial cell and the myoepithelial-like cells proliferated in the pleomorphic adenomas of salivary glands. Thus, twelve benign pleomorphic adenomas of salivary glands have been studied by electron-microscopy transmission techniques. Our analysis has proved the proliferation of two major cellular populations, one of ductal type and one of myoepithelial type, which tried to reproduce the tubulo-acinar cytoarchitecture from the normal salivary glands. We have also noticed the key role of the so-called ‘modified’ myoepithelial cells from the periphery of the proliferating epithelial units in the genesis of the myxoid and chondromyxoid tumoral stromal areas. All these ultrastructural aspects have explained the great histological diversity of these salivary gland neoplasms as well as the key role of the myoepithelial cell in its histogenesis.

The liquid scintillation counting standardization of pure-beta solutions containing pure-beta emitter impurities is a difficult task because, unlike that which can be achieved by using gamma-ray spectrometry, the continuous characteristics of beta spectra and the poor intrinsic resolution of LSC spectrometers do not allow an easy identification and precise determination of the activity concentration of these impurities. This problem was recently encountered in the standardization of a 32P solution in the framework of an international comparison, where the activity contribution of the impurities was over 10% of the main nuclide activity at the reference date. This paper describes the method used to identify the impurities in this 32P solution and the calculation of the detection efficiencies using the triple to double coincidence ratio model. Details on the calculation of the uncertainties of each activity and the covariances between these activities are given.

In prostate cancer cell lines, androgen receptor (AR) coactivators modulate the transcriptional activity of AR. However, very little is known about their expression in normal prostate tissue and during progression to cancer.AR and coactivators ARA54, ARA55, ARA70, and SRC1 RNA were analyzed by RT-PCR in normal and tumoral tissues of the same prostate, in prostate cell lines, and after hormonal treatments of prostate epithelial cells.AR-coactivators were expressed in normal and tumoral tissues and in cultured prostate cells; only ARA55 expression was decreased in tumoral relative to normal tissue of all seven prostates analyzed. It was not expressed in LNCaP and DU145 cancer cells and low in PNT2 immortalized cells in which all coactivator's expression were down regulated by DHT and up regulated by E2. In addition, coactivator's expression was increased in hyperplastic relative to normal prostate fibroblasts.ARA55 is both an AR coactivator and a focal adhesion protein (Hic-5). Its role in the progression of prostate carcinoma may therefore involve these two different functions. Its decrease in cancer tissue suggests that it plays a different role than that expected, namely, facilitate cell proliferation and therefore mobility and metastasis.

Sex determination in mammals is controlled by the SRY gene located on the Y chromosome. It encodes a protein containing a DNA-binding and DNA-bending domain. In spite of recent advances in the identification of the mechanisms that regulate male sex determination in mammals, the expression profile of the SRY protein in normal and sex-reversed human tissues is not well established. In order to localize the SRY protein and determine its cellular distribution and expression at different stages of development, we prepared monoclonal antibodies (mAb) against the recombinant SRY protein. One of these antibodies, LSRY1.1, recognizes a protein of 27 kDa in total lysates of HeLa SRYB3, a human cell line transfected with the SRY gene under the control of the SV40 promoter. Immunocytochemical analysis in the cell lines shows nuclear localization of the SRY protein. We have studied SRY protein expression in human tissues at different stage of fetal development until adult life and have demonstrated that the SRY protein is located in the nuclei of somatic cells and germ cells in the genital ridge during testis development. After testis determination, it can be detected until the adult stage in both germ cells and Sertoli cells. The presence of the SRY protein was also analyzed in biopsies of gonadal tissues of sex-reversal patients such as SRY-positive 46,XX males or SRY-positive 46,XX true hermaphrodites. SRY protein is detected in the nuclei of Sertoli cells of the testis and in the nuclei of granulosa cells in the ovotestis in these patients and in the nuclei of germ cells of both tissue types. These results suggest a common cellular origin for both Sertoli cells and granulosa cells.

We report a case study to highlight the occurrence of glioblastoma multiforme in an ovarian teratoma.A 10-year-old girl presented with a left frontal lobe primitive neuroectodermal tumour which was successfully treated. After 6 uneventful years, she developed glioblastoma multiforme located posterior to the site of the initial tumour. Six years later, she presented with a mature cystic teratoma containing glioblastoma multiforme.Glioblastoma in an ovarian teratoma is an exceptional event, which might have an initial clinical presentation as a metastatic brain tumour. Alternatively, recurring glial tumours may occur in a genetically predisposed person; the role of radiation and chemotherapy in this context remains to be elucidated.

Denys-Drash and Frasier syndromes are rare human disorders that associate nephropathy with gonadal and genital abnormalities. In DDS there is a predisposition to Wilms' tumor. Heterozygous point mutations in the Wilms' tumor, type1 gene (WT1), particularly those altering the zinc finger (ZF) encoding exons, have been reported in most DDS patients, while mutations in intron 9 of the same gene cause FS. This paper describes two cases of DDS, one FS and one patient with Wilm's tumor and intersex genitalia, in which mutations were searched by sequencing the exons 8 and 9 of WT1 gene. Patient 1 carried a missense point mutation in exon 8 (ZF2), converting a CGA-Arg codon to a TGA-stop codon. Patient 2 presented a single nucleotide deletion within exon 9 (ZF3) introducing a premature chain termination at codon 398. Patients 3 and 4 had a C--T transition at position +4 of the second alternative splice donor site of exon 9 (this mutation was detected in peripheral blood and in tumor derived DNA of patient 3). However, patient 3 had previously developed a Wilms' tumor. This is the first case of Wilms' tumor development in a phenotypically and genetically confirmed case of FS.

The two major forms of infantile persistent hyperinsulinemic hypoglycemia require different treatments, but are difficult to differentiate during surgery. Indeed, one is characterized by focal adenomatous hyperplasia often macroscopically invisible, whereas the other consists of a diffuse, but discreet, beta-cell abnormality. We evaluated, in a large series of persistent hyperinsulinemic hypoglycemia, the reliability of two criteria in differentiating these two forms: the mean beta-cell nuclear radius (MNR) and the beta-cell nuclear crowding, i.e. the number of nuclei per 1000 micron 2 beta-cell (BCNC). The values of the largest MNR and of BCNC in cases bearing a focal lesion (respectively, 3.27 microns +/- 0.25 and 14.62 +/- 1.78) were significantly different from those in the diffuse pathology (4.25 microns +/- 0.43 and 10.00 +/- 1.55). Setting the threshold value of MNR at 3.70 microns and that of BCNC at 12.00 enabled correct classification of 90.9% of the diffuse and 100% of the focal forms. beta-Cell nuclear analysis can thus contribute to a subclassification of the syndrome, not allowed by clinical or biological data. If performed during surgery it could help in determining the extent of pancreatectomy necessary to cure the patient, as the diffuse form, with abnormal nuclei in the whole pancreas, requires subtotal to near-total pancreatectomy, whereas the focal form, devoid of abnormal insular beta-cell nuclei, can be cured by partial pancreatectomy.

We report the case of a systemic infection due to Stomatococcus mucilaginosus with cutaneous localisations occurring in a neutropenic child. The histological features of this cutaneous involvement are very unusual and the diagnosis can be suggested before bacteriological results.

The Internet network is the largest computer network in the world. It can be accessed by a telephone line and a modem. Its different functions are the electronic mail (e-mail), the discussion forums ("newsgroups"), the transfer of files and the navigation between "hypertext" pages ("World Wide Web"). This network offers multiple services for pathology: access to databases, consultation of image banks or electronic journals, teleteaching, informations about congresses and societies, participation to thematic forums. We have connected to this network on October 1995 a french-english web site called "Anapath Web" (http://www.anapath.necker.fr) devoted to pathology. Its purpose is to collect information useful to pathologists and to develop specific applications. We are conceiving several projects for teleteaching.

Anti-Müllerian hormone (AMH) immunoreactivity was studied on paraffin sections obtained from archival testicular biopsies of 29 children with intersex disorders and of 22 controls. Strong AMH immunoreactivity was observed in Sertoli cell cytoplasm from 8 fetal weeks until puberty. During pubertal maturation, in both normal and intersex patients, AMH expression was present in premeiotic seminiferous tubules, but was no longer detected in neighboring tubules with meiotic development. AMH immunostaining was abolished in the testis of one patient with persistent Müllerian ducts due to a mutation of the AMH gene, but was conserved in the testes of two patients with mutations of the AMH receptor gene. Testicular dysgenesis usually results in sexual ambiguity, with low testosterone and AMH serum levels and persistence of Müllerian derivatives. AMH immunoreactivity was conserved in premeiotic seminiferous tubules of dysgenetic testes, and also in sex-cord cells of a gonadoblastoma. In patients with asymmetric gonadal differentiation, the streak gonad was AMH-negative. In conclusion, secretion of AMH is a constitutive feature of the immature Sertoli cell and its expression is altered only by mutations of the AMH gene, but not by gonadal dysgenesis. The degree of regression of Müllerian ducts and serum AMH levels reflect the number, not the functional value, of Sertoli cells present in the immature testis.

The diagnosis and management of 22 patients with true hermaphroditism are described. Sixteen of them were first seen before the age of 4 months. The initial manifestations were ambiguous genitalia in 20 cases (two of them identified prenatally by ultrasound examination), isolated clitoromegaly in one, and penile hypospadias plus unilateral cryptorchidism in one. All patients but one had at least one palpable gonad. Eleven of the twelve patients examined before the age of 6 months had basal plasma testosterone levels >0.4 ng/ml. In older patients the stimulation test was necessary to demonstrate male testosterone secretion. The most common peripheral karyotype was 46,XX (17 cases); the other karyotypes were 47,XXY (1 case) and mosaicism 46,XX/46,XY (2 cases) or 46,XX/47,XXY (2 cases). One of the patients with the 46,XX karyotype had 46,XX/46,XY on fibroblast culture; four had the SRY gene in their leukocytes and one in the tissue taken at gonadal biopsy. A vagina was found in all patients at laparotomy, and a uterus was found in 17 cases (as a hemiuterus in 9). Genitography failed to demonstrate a uterus in only one case. The testicular tissue was dysgenetic but the ovarian tissue was normal. Sex assignment was male in 8 patients (reoriented by us in 2) and female in 14 patients (reoriented by us in 3). Spontaneous pubertal development occurred in the 4 patients (2 boys, 2 girls) with gonadal tissue who reached pubertal age. We conclude that true hermaphroditism is a heterogeneous condition in terms of its genetic background, with a prevalence of the 46,XX karyotype. There may be mosaicism with a Y-bearing cell line limited to the gonad (its frequency is probably underestimated), a paternal meiotic exchange between X and Y occurring in 46,XX cases with SRY , or a lack of the SRY gene, suggesting that other genes working independently of SRY may also determine testicular differentiation. (J P EDIATR 1994;125:738-44)

Pulmonary blastoma is a tumor with bad prognosis that is exceptionally seen before the age of 2 years.A 3 1/2 month-old infant was admitted because she suffered from tachypnea. A left pneumothorax with shift of the mediastinum was recognized that required insertion of a chest tube followed by ventilation and pleural drainage. X rays and CT scan showed a round bullous lesion in the left lung that persisted at the age of 5 months. At that time, clinical deterioration led to thoracotomy allowing excision of a bullous tumor; histological examination showed that this tumor was a pulmonary blastoma. Recurrence of this tumor, 16 months later, required chemotherapy and surgical excision. The patient is normal at the age of 4 years.Pulmonary blastoma is exceptional in infancy; it may be revealed by pneumothorax. Its bad prognosis requires aggressive therapy.

During mammalian embryogenesis, the presence of the SRY gene determines the bipotential gonad to develop as a testis. 46,XY sex reversal has been described in man. It is associated with an essentially female phenotype and a streak gonad. In a collaborative study, we analysed 36 patients with a 46,XY sex reversal. The testis determining region of the Y chromosome was analysed by Southern blotting and by DGGE analysis of the SRY open reading frame (orf). We found a total of 7 mutations in the testis determining region including the SRY gene. This brings to 19 the total number of mutations in SRY associated with sex reversal. No relationship was found between the SRY status and the presence or absence of gonadoblastoma. However, a correlation was observed between the SRY genotype and the histology of the gonad. A mutant in SRY is associated with a completely dysgenetic gonad. The presence of immature testicular tubules is usually observed when SRY is normal. These latter results suggest the existence of as yet unidentified testis determining genes.

Myxoma, a benign cardiac tumor, develops in intracavitary locations. It is most frequent in the left atrium, but rare in the pulmonary infundibulum.An 18 month-old girl suddenly became cyanotic during playing and lost consciousness. Resuscitation was ineffective. Post-mortem examination showed diffuse pulmonary edema and multiple small pulmonary emboli. There was a myxoma of the septal wall of pulmonary infundibulum and histological examination showed that the infundibulum and the pulmonary valve were completely infiltrated by myxoid tissue.The death of this girl was probably due to a sudden embolism of blood clots developed in contact with the myxoma. This case emphasizes the need for pathologic investigation in all cases of sudden death.

The human testis-determining gene was recently isolated from a 35 kb region on the human Y chromosome which was present in four sex-reversed individuals, three XX males and one true hermaphrodite. One of the XX males and the true hermaphrodite were sibs. A more detailed molecular analysis of these two patients and their family for Y-DNA sequences including the testis-determining gene, SRY was performed. The father was found to harbor two copies of SRY, one on his Y chromosome and the other on his X chromosome located at Xp22 determined by in situ hybridization. Somatic cell hybrids were generated from peripheral blood lymphocytes. Analysis of Y chromosome-negative somatic cell hybrids from the XX male, the true hermaphrodite and their father, revealed that both the X and Y pseudo-autosomal boundaries were present. The present of both boundaries suggests than an unequal interchange of X and Y material occurred with the cross-over breakpoint located within the X pseudo-autosomal region. The paternal SRY-bearing X chromosome was transmitted to two of his children, a 46 XX true hermaphrodite and a 46,XX male. The presence of SRY on an X chromosome associated with two sex phenotypes strongly suggests that the phenotypic variability was caused by differential inactivation of the SRY-bearing X chromosome, thereby influencing SRY expression.

Three pediatric cases of parotid carcinoma are reported two are acinic cell carcinoma of relatively good prognosis. The third case is a cystic variety of salivary duct carcinoma, more exceptional, which prognosis remains uncertain. A review of the parotid tumors of this age range is done.

To investigate the relation between lung function and inflammation and fibrosis in patients with diffuse lung fibrosis, a study was made of untreated patients without appreciable airway obstruction (14 patients with cryptogenic fibrosing alveolitis and seven with pneumoconiosis). Quantitative assessment of inflammatory infiltration and fibrosis was carried out on open lung biopsy specimens and compared with lung volumes, carbon monoxide transfer factor (TLCO), TLCO corrected for alveolar volume (TLCO/VA), and arterial blood gases at rest and during exercise. The degree of fibrosis and the degree of cellular infiltration were positively correlated. Lung volumes and TLCO were correlated with the grades of fibrosis and cellular infiltration of alveoli; arterial blood gases during exercise tended to correlate with both fibrosis and infiltration (p less than 0.06). In contrast, morphological data were not correlated with gas exchange at rest or with TLCO/VA. It is concluded that, in untreated patients with diffuse lung fibrosis, lung volumes, TLCO, and arterial blood gases during exercise reflect the lung lesions, and that the pulmonary function tests used cannot discriminate between fibrosis and infiltration of the lung by inflammatory cells.

A case of solitary plasmacytoma of the trachea is reported. Immunohistochemical study is mandatory to prove a monoclonal immunophenotyping. Research for signs of systemic disease and follow up over a long period of time are indicated. Surgery alone, sometimes followed by irradiation, seem to be the treatment of choice. In most cases, complete resolution is observed.

Systemic mastocytosis is an uncommon disorder due to multiorgan infiltration by mast cells. The authors report the case of a man whose mastocytosis was revealed in an unusual way by hepatomegaly and portal hypertension of the sinusoidal type. This case was also characterized by the absence of urticaria pigmentosa, the presence of seborrheic warts in which mast cell infiltration was noted and the absence of digestive symptoms. The peculiarities of this case are compared to the published data.