Evaluation of encephalic ventricular volume from the magnetic resonance imaging scans of thirty-eight human subjects

Summary Accurate volume determination of the encephalic ventricles is of importance in several clinical conditions, including Alzheimer's presenile dementia, schizophrenia, and benign intracranial hypertension. Previous studies have investigated the accuracy with which magnetic resonance imaging (MRI) can be used in clinical practice to evaluate the encephalic ventricles. However, adequate evaluation of pathological conditions depends on a sufficient amount of morphometric data from normal subjects. To begin establishing this data base for normal subjects, we evaluated the MRI scans of 38 subjects found to have no apparent pathology and calculated the ventricular volume in each case by using methods previously developed in our laboratory. The results were then compared with published volumes determined from studies that used either ventricular casts or computerized tomographic scans. The average total ventricular volume for all 38 subjects was 17.4 cm³, while that for males was 16.3 cm³ and that for females was 18.0 cm³. A small but significant correlation was found between age of subject and ventricular volume, with ventricular size increasing with age.

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Evaluation du volume des ventricules cérébraux à partir des images obtenues en résonance magnétique nucléaire chez 38 sujets humains

Résumé La détermination exacte du volume des ventricules cérébraux est importante en clinique comme par exemple dans la démence présénile d'Alzheimer, la schizophrénie et l'hypertension intracrânienne bénigne. Des études antérieures ont étudié la fiabilité de la résonance magnétique nucléaire en pratique clinique pour évaluer le volume des ventricules cérébraux. Toutefois une évaluation correcte dans les conditions pathologiques implique une bonne connaissance des données morphométriques du sujet normal. Pour établir ces données sur « le sujet normal », nous avons étudié les coupes obtenues en IRM chez 38 sujets apparemment indemnes de toute pathologie; nous avons calculé le volume ventriculaire dans chaque cas en utilisant des méthodes mises au point auparavant dans notre laboratoire. Les résultats ont été ensuite comparés avec ceux obtenus par d'autres études utilisant soit des moules ventriculaires, soit des coupes tomographiques computérisées. Le volume ventriculaire total moyen chez 38 sujets est de 17,4 cm³, mais il est chez les sujets masculins de 16,3 cm³ et chez les sujets de sexe féminin de 18 cm³. Une corrélation faible mais significative a été trouvée entre l'âge du sujet et le volume ventriculaire, étant entendu que la taille du ventricule augmente avec l'âge.

     

Simultaneous detection of antibodies to cytomegalovirus and herpes simplex virus by using flow cytometry and a microsphere-based fluorescence immunoassay.

A sensitive assay for the simultaneous detection of anti-cytomegalovirus and anti-herpes simplex virus antibodies was developed. Two different sizes of polystyrene microspheres were coated with purified viral antigens. Human antiviral antibodies were detected with a biotin-streptavidin amplification procedure with phycoerythrin as the fluorescent label. Microsphere-associated fluorescence was quantitated with a flow cytometer. Sixteen percent of samples initially scored as seronegative for cytomegalovirus and 35% of samples initially scored as seronegative for herpes simplex virus by conventional assays were clearly found positive by the microsphere technique. This flow cytometric assay can simultaneously detect several specific antibodies at levels which are below the sensitivity of standard assays. The dynamic range of this assay is at least sixfold greater than that of enzyme immunoassays. This technique is amenable to numerous serologic assays and could greatly expand the clinical laboratory applications of flow cytometry.     

Biology of Hyalomma impeltatum (Acari: Ixodidae) under laboratory conditions

Completion of the life cycle of Hyalomma impeltatum Schulze & Schlottke required an average of 108 d at 26 +/- 1 degree C, 92-96% RH, and 12:12 (L:D) photoperiod. Weights of unfed larvae, nymphs, and females were 0.02, 0.16, and 15.4 mg, respectively, and increased 23-, 164-, and 55-fold, respectively, as a result of feeding on guinea pigs. Larvae and adults exhibited host-seeking behavior less than 1 d after hatching and molt, respectively; nymphs exhibited host-seeking behavior 2.9 d after molt. The mean (+/- SE) feeding period as larvae was 5.9 (+/- 2.23) d, nymphs 6.7 (+/- 1.10) d, and females 8.0 (+/- 0.19) d. Larvae molted 12.4 (+/- 0.26) d and nymphs molted 28.9 (+/- 0.22) d after engorgement. A sex ratio of 1.26:1 female/male was determined from emerged adults. Females began oviposition 8.9 (+/- 0.22) d after engorgement and produced 10,680 (+/- 300) eggs per female. Egg hatch was 84% (+/- 2.68) after an incubation period of 32.8 (+/- 0.19) d. Females converted 55% of engorged weight into eggs and produced 12,475 (+/- 188) eggs/g of engorged body weight. A freshly laid egg on the first day of oviposition weighted 47.7 (+/- 0.65) micrograms. An inverse relationship between egg weight and rate of egg production was observed.     

Development of an antibody that binds sulfur mustard.

An antibody that binds bis(2-chloroethyl) sulfide (sulfur mustard) was developed. The immunizing antigen was prepared from the hapten 4-(2-chloroethyl)benzoic acid covalently bound to keyhole limpet hemocyanin (KLH). The antibody was monitored by a solid phase enzyme-linked immunosorbent assay (ELISA). The test antigen consisted of a second hapten, 8-chlorocaprylic acid, covalently bound to bovine serum albumin (BSA). The test antigen was absorbed to the wells of 96-well plates. The immunizing and test antigens contain a common chloroethyl moiety. Thiodiglycol, the principal hydrolysis product of sulfur mustard, does not react with the antibody. This antibody, because of its specificity, has the potential to be a valuable tool for mustard research and forensic detection.     

Inflammatory cell infiltrate in a responding metastatic nodule after vaccine-based immunotherapy

A patient with von Hippel Lindau disease, bilateral symmetric renal cell carcinoma and pulmonary metastases treated with immunotherapy is the subject of this study. A left kidney and tumour mass were removed and the tumour cells used to make an autologous tumour/bacille Calmette–Guérin (BCG) vaccine as part of the treatment protocol. The patient's pulmonary nodules responded, but the remaining renal nodule subsequently grew. Samples of both tumours were obtained allowing for an internally controlled evaluation of the histological and immunohistologic differences between a responding and non-responding tumour nodule after therapy. The immunotherapy protocol is designed to promote a T cell response to autologous tumour. Cellular infiltrates were demonstrated in both responding and non-responding nodules compared with the pretreatment tumour specimen, but the responding nodule contained proportionately more T cells as well as markedly increased numbers of plasma cells and granulocytes. This suggested that several arms of the immune system may have been operative in the responding nodule.     

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.      

Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities

An RNA-binding motif (RBM) gene family has been identified on the human Y chromosome that maps to the same deletion interval as the 'azoospermia factor' (AZF). We have identified the homologous gene family (Rbm) on the mouse Y with a view to investigating the proposal that this gene family plays a role in spermatogenesis. At least 25 and probably >50 copies of Rbm are present on the mouse Y chromosome short arm located between Sry and the centromere. As in the human, a role in spermatogenesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expression between the two species. Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are female due to a position effect resulting in non-expression of Sry ; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, making this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis. Most of the copies of Rbm map to this deletion interval, and the Yd1males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development. In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm anomalies; however, the different effects of deletion are consistent with the differences in expression between the two species.      

ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome

It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.      

Recurrent Poisoning in Children: A Review

The literature on poisoning accidents or ingestion of toxicsubstances in children is reviewed. Special emphasis is givento the phenomenon of recurrent or repeat episodes. Recommendationsare made concerning means for identifying children who are atrisk for repeat poison episodes, as well as for developing methodsof intervention to prevent such occurrences.     

Blurring artifacts in megavoltage radiography with a flat-panel imaging system: comparison of Monte Carlo simulations with measurements

Originally designed for use at medical-imaging x-ray energies, imaging systems comprising scintillating screens and amorphous Si detectors are also used at the megavoltage photon energies typical of portal imaging and industrial radiography. While image blur at medical-imaging x-ray energies is strongly influenced both by K-shell fluorescence and by the transport of optical photons within the scintillator layer, at higher photon energies the image blur is dominated by radiation scattered from the detector housing and internal support structures. We use Monte Carlo methods to study the blurring in a notional detector: a series of semi-infinite layers with material compositions, thicknesses, and densities similar to those of a commercially available flat-panel amorphous Si detector system comprising a protective housing, a gadolinium oxysulfide scintillator screen, and associated electronics. We find that the image blurring, as described by a point-spread function (PSF), has three length scales. The first component, with a submillimeter length scale, arises from electron scatter within the scintillator and detection electronics. The second component, with a millimeter-to-centimeter length scale, arises from electrons produced in the front cover of the detector. The third component, with a length scale of tens of centimeters, arises from photon scatter by the back cover of the detector. The relative contributions of each of these components to the overall PSF vary with incident photon energy. We present an algorithm that includes the energy-dependent sensitivity and energy-dependent PSF within a ray-tracing formalism. We find quantitative agreement (approximately 2%) between predicted radiographs with radiographs of copper step wedges, taken with a 9 MV bremsstrahlung source and a commercially available flat-panel system. The measured radiographs show the blurring artifacts expected from both the millimeter-scale electron transport and from the tens-of-centimeters length scale arising from the scattered photon transport. Calculations indicate that neglect of the energy-dependent blurring would lead to discrepancies in the apparent transmission of these wedges of the order of 9%.