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Multi-detector CT angiography of the intra-cranial circulation: normal anatomy and pathology with angiographic correlation.

Multidetector computed tomography angiography (MD-CTA) of the intra-cranial circulation shows great potential in the evaluation of intra-cranial vascular disease. Interpreting these studies requires a detailed knowledge of the technique, its advantages and disadvantages, as well as a strong understanding of normal intra-cranial vascular anatomy. The purpose of this review is to describe the technique for MD-CTA, demonstrate normal anatomy, anatomic variants and vascular pathology with an emphasis on aneurysms.

Brain Diseases↗

Phylogeny of immunoglobulin structure and function. XIV. Peptide map and amino acid composition studies of shark antibody light chains.

Light chains from antibodies to the streptococcal A-variant carbohydrate from individual nurse sharks were compared by peptide maps of tryptic digests and amino acid compositions. Although the amino acid compositions of the different chains were quite similar, considerable differences as well as similarities were demonstrable on peptide maps. The peptide maps were interpreted as indicating that shark L chains likely have constant and variable regions as seen in the immunoglobulins of higher animals. Furthermore the unique peptides characteristic of different L chains support the hypothesis that nurse sharks, as a species, possess a relatively large number of different L chain amino acid sequences which are compatible with antibody binding sites to the streptococcal antigen. Hence the repetoire of nurse shark antibody combining sites to this antigen appears to be quite extensive.

Amino Acid Sequence↗

Molybdenum chalcogenobenzimidato complexes: radical synthesis and nitrile extrusion via beta-EPh (E = S, Se, and Te) elimination.

Molybdenum chalcogenobenzimidates of formula (Ph[PhE]C=N)Mo(N[t-Bu]Ar)(3) (Ar = 3,5-C(6)H(3)Me(2)) have been obtained by treatment of Mo(N[t-Bu]Ar)(3) sequentially with benzonitrile and 0.5 equiv of PhEEPh (E = S, Se, and Te). Molecular structure determinations have been carried out for the S and Se variants. The Te variant extrudes PhCN forming structurally characterized (PhTe)Mo(N[t-Bu]Ar)(3) with facility assessed via stopped-flow kinetic measurements, while the Se and S analogues exhibit increasing stability. Quantum chemical calculations and solution calorimetry have been employed as an aid to interpretation of the PhCN extrusion reaction.

Journal Article↗

Chromokinetics of metabolic pathways.

Some methods to study and intuitively understand steady-state flows in complicated metabolic pathways are discussed. For this purpose, a suitable decomposition of complex metabolic schemes into smaller subsystems is used. These independent subsystems are then interpreted as basic colors of a chromatic coloring scheme. The mixture of these basic colors allows an intuitive picture of how a steady state in a metabolic pathway can be understood. Furthermore, actions of drugs can be more easily investigated on this basis. An anaerobic variant of pyruvate metabolism in rat liver mitochondria is presented as a simple example. This experiment allows measurement of the percentage that each basic color contributes to the steady states resulting from different experimental conditions. Possible implementations of existing algorithms and rational design of new drugs are discussed. A MATHEMATICA program, based on a new algorithm for finding all basic colors of stoichiometric networks, is included.

Algorithms↗

Case-control genetic association studies in gastrointestinal disease: review and recommendations.

As our knowledge of genetic variation grows, our ability to use this information to unravel the mysteries of human disease expands. Identification of genes and inexpensive methods to sequence them has resulted in a rising interest in evaluating specific variants and whether they may result in clinical manifestations or symptoms. Genetic variants include restriction fragment length polymorphisms, variable number tandem repeats, DNA microsatellites, and single nucleotide polymorphisms. Using these variants, genetic association studies, also referred to as candidate gene association or genotype-disease association studies are being performed by clinical and basic researchers alike. They are relatively easy to perform, but as a result of their deceivingly simple design, can be conducted or interpreted poorly. A positive association between a genotype and a GI disease of interest may be because the genotype causes (or increases susceptibility to) the disease, but may also be the result of the genotype being in linkage disequilibrium with the actual disease susceptibility gene, or be a false positive due to chance or bias in study design. An excellent understanding of the genetic and methodological issues surrounding these studies is therefore essential. We provide an overview of terminology and provide insight into the complexities underlying these studies. Recommendations for reporting the results of a genetic association study are provided to assist with study planning and manuscript preparation.

Case-Control Studies↗

The dentinogenic ghost cell tumor.

An unusual case and they of dentinogenic ghost cell tumor, a peculiar variant of calcifying odontogenic cyst, is reported. The tumor consisted predominantly of ghost cells with occasional areas of "dentinoid" in close proximity to masses of ghost cells. The presence of ameloblastoma-like nests of epithelium was characteristic of the present case and they were interpreted as a degenerative phenomenon exhibiting an inductive effect with formation of abundant ghost cells, occurring within a pre-existing ameloblastoma. The term of "dentinogenic ghost cell tumor" is employed for this unique lesion presented in this report. The literature describing the neoplastic potential of the calcifying odontogenic cyst is briefly reviewed.

Adult↗

A lipooligosaccharide-binding site on HepG2 cells similar to the gonococcal opacity-associated surface protein Opa.

The lacto-N-neotetraose-containing lipooligosaccharide (LOS) present on the surface of most Neisseria gonorrhoeae organisms may serve many important functions in gonococcal pathogenesis. This surface glycolipid contains the cross-reactive epitope to human paragloboside and can be sialylated by gonococci grown in the presence of CMP-N-acetylneuraminic acid. Another possible role for this glycolipid could be to mimic human asialocarbohydrates and act as a ligand for asialoglycoprotein receptors contained on numerous human cells. The most noted of this large family of receptors is that expressed on the surface of hepatic cells. In a model cell system, using the hepatoma tissue culture cell line HepG2, we wanted to investigate if the presence of this asialoglycoprotein receptor influenced the adherence and/or invasion of gonococci expressing the lacto-N-neotetraose structure. Piliated variants of the gonococcal wild-type strain 1291 and its isogeneic LOS mutant 1291E were used in adherence-invasion assays. This gonococcal strain is somewhat unusual in that it expresses large amounts of predominantly one species of LOS, thus reducing the complexity of interpreting the data. The data from these assays suggested that the Gal(beta 1-4)GlcNAc(beta 1-3)Gal(beta 1-4)Glc carbohydrate structure on the wild-type LOS affected the adherence-invasion of gonococci into the HepG2 cells. In studies to determine whether the major hepatic asialoglycoprotein receptor was involved in these interactions, we found that the HepG2 cells contained two receptors which bound gonococcal LOS. One of these was the asialoglycoprotein receptor, and the data concerning this receptor will be reported elsewhere. The data on the second receptor are reported here. Purified, 125I-labeled gonococcal LOS was used to identify specific high-affinity LOS-binding sites. These binding experiments revealed one major binding site corresponding to a protein with a molecular mass of 70 kDa (p70). Several lines of evidence in this study suggested that the oligosaccharide region of LOS played an important role in LOS binding to the p70 of HepG2 cells. In addition, we show that this human LOS receptor has some similarities to the gonococcal Opa proteins.

Antigens, Bacterial↗

[Immunoradionuclide localization of human neuroblastoma xenografted in nude mice using anti-GD2 labelled with I125].

Neuroblastoma is the most frequent tumour of the childhood under the age of 5. The staging and the follow up are achieved by MIBG scintigraphy, considered as the method of reference, but sometimes difficult to interpret . The availability of monoclonal antibodies against the ganglioside GD2, expressed on the cell membrane of neuroblastoma and neuro-endocrine cancers offers novel tools that deserve to be carefully explored. We investigated four mouse monoclonal antibodies (3 IgG3: BW704, 7A4, 60C3, and the IgG1 variant of BW704: MAK704), on nude mice xenografted with a human neuroblastoma (REM). Sixty one nude mice were included. The three former MAbs provided tumour imaging, the best results being obtained with BW704, followed by 7A4 and 60C3. MAK704 was disappointing. A control antiphosphorylcholine antibody (P51-1) did not give any tumour image in the three tested mice. Scintigraphy ratios tumour/liver and tumour/muscle reached 20 and 100 with BW704, respectively, on the 10th day. Good imaging quality was already obtained from the 24th h. The tumour uptake, calculated from radioactivity countings of resected samples, reached 22 +/- 3% of injected dose per gramme. These results let us hope that these antibodies could also provide highly contrasted images in humans and could open the way for therapeutic applications.

Animals↗

Intracranial stenoocclusive disease: MR angiography with magnetization transfer and variable flip angle.

PURPOSE: To assess time-of-flight MR angiography that uses magnetization transfer contrast (MTC) pulses, tilted optimized nonsaturating excitation (TONE), and a 256 x 512 image matrix for the detection of small intracranial arteries and for the detection and quantification of intracranial arterial stenoocclusive disease. METHODS: To assess anatomic sensitivity, six interpreters, in a blinded fashion, reviewed the MTC/TONE MR angiograms and selective intraarterial angiograms obtained in 70 patients within a mean interval of 5.5 days (SD, 1.5). In addition, all intracranial angiograms were evaluated with regard to presence and degree of arterial stenosis and anatomic variants. RESULTS: Interobserver correlations for determining vessel length were comparably high for both methods. A strong correlation was found between measurements obtained on MR angiograms and those obtained on intraarterial angiograms. The mean vascular length averaged across all arteries was 34.8 mm (SD, 28.1) on MR angiograms and 53.2 mm (SD, 36.8) on intraarterial angiograms. Forty-one stenoses and occlusions and 30 anatomic variants were identified with intraarterial angiography. All arterial variants and 100% of occluded vessels were graded correctly. Moreover, 80% of stenoses greater than 70% and 88% of stenoses less than 70% were quantified correctly at MR angiography. Specificity for identifying stenotic disease was 99%. CONCLUSION: Despite inferior display of vessel length, MTC/TONE MR angiography with increased spatial resolution was able to show the vast majority of high grade lesions visible at selective intraarterial angiography and may suffice for clinical decision making in many patients.

Adolescent↗

Comparison of neutralizing epitopes among infectious bursal disease viruses using radioimmunoprecipitation.

Monoclonal antibodies (MAbs) were used to analyze the relatedness of neutralizing epitopes of infectious bursal disease virus (IBDV) strains. The MAb B69 neutralized the homologous D78 virus but not the MD and Del-A variant strains of IBDV. MAbs 33E8 and R63 neutralized D78 and variant strains MD and Del-A. A cDNA clone consisting of a 1000-base-pair fragment of the VP2 gene from the Del-A IBDV strain was translated using an in vitro system. Six peptides were observed following translation, which represented a full-length product (35.5 kilodaltons) and five truncated products. The translated peptides were radioimmunoprecipitated using MAbs B69, 33E8, and R63. Only MAb R63 immunoprecipitated the in vitro translation products from Del-A. MAbs B69 and 33E8 did not immunoprecipitate the in vitro-translated VP2 peptides. The D78 and Del-A viruses were radiolabeled in vivo using 35S-methionine. Proteins from these viruses were examined by radioimmuno-precipitation with MAbs B69, 33E8, and R63. Although the background made interpretation of the results difficult for MAb B69, this MAb clearly immunoprecipitated VP2 of D78. MAb 33E8 immunoprecipitated the D78 VP3 protein, and R63 immunoprecipitated the VP2 protein. MAb R63 also immunoprecipitated the 35S-methionine-labeled VP2 protein from Del-A. It was concluded that the neutralizing epitope represented by 33E8 was located on VP3 and that the epitope represented by R63 is located on both classic and variant viruses in the region of VP2 that is generally thought to contain sequence variability among IBDV strains.

Antigens, Viral↗

Arterial compression of the right common iliac vein; an unusual anatomical variant.

Compression of the left common iliac vein by the right common iliac artery has been well described (Cockett's syndrome). The authors describe a case report of compression of the right common iliac vein by the right internal iliac artery. The patient presented with ipsilateral lower limb oedema. Venography showed smooth extrinsic compression of the right common iliac vein. The CT scan was initially interpreted as showing no extrinsic mass or obvious compressing lesion and lymphography was normal. It was the duplex scan which showed the bifurcation of the right common iliac artery crossing the right common iliac vein and causing significant extrinsic compression.

Cardiovascular Abnormalities↗

The origins of the Polynesians: an interpretation from mitochondrial lineage analysis.

Using mitochondrial lineage analysis of 1,178 individuals from Polynesia, the western Pacific, and Taiwan, we show that the major prehistoric settlement of Polynesia was from the west and involved two or possibly three genetically distinct populations. The predominant lineage group, accounting for 94% of Polynesian mtDNA, shares a 9-bp COII/tRNA(Lys) intergenic deletion and characteristic control region transition variants, compared to the Cambridge reference sequence. In Polynesia, the diversity of this group is extremely restricted, while related lineages in Indonesia, the Philippines, and Taiwan are increasingly diverse. This suggests a relatively recent major eastward expansion into Polynesia, perhaps originating from Taiwan, in agreement with archeological and linguistic evidence, but which experienced one or more severe population bottlenecks. The second mitochondrial lineage group, accounting for 3.5% of Polynesian mtDNA haplotypes, does not have the 9-bp deletion and its characterized by an A-C transversional variant at nt position 16265. Specific oligonucleotides for this variant were used to select individuals from the population sample who, with other sequences, show that the Polynesian lineages were part of a diverse group in Vanuatu and Papua New Guinea. The very low overall diversity of both lineage groups in Polynesia suggests there was severe population restriction during the colonization of remote Oceania. A third group, represented by only four individuals (0.6%) in Polynesia but also present in the Philippines, shares variants at nt positions 16172 and 16304. Two Polynesians had unrelated haplotypes matching published sequences from native South Americans, which may be the first genetic evidence of prehistoric human contact between Polynesia and South America.

Base Sequence↗

Evaluation and use of the white blood cell differential provided by the Coulter STKS in a children's hospital.

The Coulter STKS was evaluated in a children's hospital, in order to (a) compare the WBC differential given by the instrument to a 400 cell visual differential (reference method); (b) evaluate the sensitivity and specificity of the alarm system, and (c) provide data concerning the use and interpretation of results in children. 653 blood samples were collected. The Coulter STKS results were studied in 523 patients having no morphological abnormalities in the blood smears, separated into subgroups according to the presence of STKS alarms and according to age. The results were found accurate both in STKS negative and STKS positive patients (i.e., those with alarms: 'Blasts', Imm Gran 2, Variant Lymph, NRBC, review slide). Negative STKS results had the same accuracy in all age groups, except in neonates where slide review must be systematically performed. The instrument exhibited a good sensitivity of the suspect flags studied (91.4%), with a lower specificity (72%) reflecting the number of false positive results found in our group, probably due to the cytological features particular to children. However, it was shown that the numerical results given by the Coulter STKS in positive patients could be taken into account, provided that a scan of the blood smear was negative for morphological WBC abnormalities.

Adolescent↗

Histological and cytogenetic findings in a malignant tumor of the chest wall and lung (Askin tumor).

This report describes a histological and cytogenetic study of a malignant tumor involving the chest wall and lung (Askin tumor) of a young girl. Although initially considered to represent a variant of Ewing's sarcoma, immunocytochemical studies disclosed neuron-specific enolase in neoplastic cells. Ultrastructural study revealed rare cells which contained microtubules and/or dense core neurosecretory type granules. Cytogenetic analysis of neoplastic cells disclosed a reciprocal translocation (11;22)(q24;q12) and occasional extrachromosomal structures interpreted as double minute chromosomes. The latter finding, an indication of gene amplification, is commonly identified in neural crest-derived neoplasms. These ultrastructural, immunocytochemical, and karyotypic data provide evidence in support of a neuroepithelial histogenesis for the Askin tumor.

Child↗

Irregular polymerase chain reaction-sequence-specific oligonucleotide hybridization patterns reveal seven new HLA-DRB1 alleles related to DR2, DR3, DR6, DR8, and DR11. Implications for sequence-specific priming.

In the past 3 years we have typed over 7000 individuals for HLA-DRB using a nonradioactive PCR-SSO method. The use of locally developed computer programs simplified data input and the interpretation of the DRB PCR-SSO readings. In this way we detected a number of samples with unexpected hybridization patterns. DRB1 exon 2 segments of these samples were amplified, cloned, and sequenced and appeared to identify seven new DRB alleles: DRB1*0304, a DRB1*0301 variant, was observed in three unrelated Caucasoid individuals; DRB1*1606, which is very similar to *1603; DRB1*1113 is a *1101 variant with some *1401 sequences; DRB1*1310 is *1301-like; DRB1*1311 is similar to *1305 and *1307; DRB1*1416 is a *1401 sequence with a HV3 derived from *1301; DRB1*0808 was found in an Ethiopian individual. Next, we studied the effectiveness of PCR-SSP typing of the newly defined DRB1 alleles. Only two variants were distinguished as odd by PCR-SSP and two were typed as regular specificities. Three alleles were not amplified by the primer sets used. As compared to PCR-SSO, the PCR-SSP typing method using currently available typing kits clearly has limitations as far as the recognition of new and variant alleles is concerned. The products of some of these new alleles may be distinguished using conventional serology.

Alleles↗

Association between c135G/A genotype and RET proto-oncogene germline mutations and phenotype of Hirschsprung's disease.

BACKGROUND: Several genes, including the major susceptibility gene RET, have roles in development of Hirschsprung's disease. Results of genetic-linkage analysis of patients with familial disease with both long-segment and short-segment phenotypes have shown close linkage with the RET locus. We aimed to investigate whether both RET mutations and polymorphisms contribute to phenotype of Hirschsprung's disease. METHODS: We looked at the coding region of all 21 exons of the RET proto-oncogene, including the flanking intronic sequences, by direct DNA sequencing in 76 caucasians from Germany with Hirschsprung's disease. FINDINGS: 20 different mutations were detected in 18 patients. Mutations were under-represented in patients with a homozygous RET c135A/A genotype in association with short-segment phenotype. Short-segment phenotype also arose if the RET mutation was on the c135A allele; conversely, a RET germline mutation on the c135G allele resulted in long-segment phenotype, particularly in heterozygous c135G/A patients. INTERPRETATION: These observations lend support to the idea that both RET alleles have a role in pathogenesis of Hirschsprung's disease, in a dose-dependent fashion. We also showed that the c135G/A polymorphism modifies the phenotype by a within-gene interaction between the c135A variant and a mutation.

Alleles↗

Soft vector quantization and the EM algorithm.

The relation between hard c-means (HCM), fuzzy c-means (FCM), fuzzy learning vector quantization (FLVQ), soft competition scheme (SCS) of [Yair et al. (1992)] and probabilistic Gaussian mixtures (GM) have been pointed out recently by [Bezdek and Pal (1995)]. We extend this relation to their training, showing that learning rules by these models to estimate the cluster centers can be seen as approximations to the expectation-maximization (EM) method as applied to Gaussian mixtures. HCM and unsupervised, LVQ use 1-of-c type competition. In FCM and FLVQ, membership is the -2/(m-1)th power of the distance. In SCS and GM, Gaussian function is used. If the Gaussian membership function is used, the weighted within-groups sum of squared errors used as the fuzzy objective function corresponds to the maximum likelihood estimate in Gaussian mixtures with equal priors and covariances. The fuzzy clustering method named fuzzy c-means alternating optimization procedure (FCM-AO) proposed to optimize the former is then equivalent to batch EM and SCS's update rule is a variant of the online version of EM. The advantages of the probabilistic framework are: (i) we no longer have spurious spread parameters that needs fine tuning as m in fuzzy vector quantization or beta in SCS; instead we have a variance term that has a sound interpretation and that can be estimated from the sample; (ii) EM guarantees that the likelihood does not decrease, thus it converges to the nearest local optimum; (iii) EM also allows us to estimate the underlying distance norm and the cluster priors which we could not with the other approaches. We compare Gaussian mixtures trained with EM with LVQ (HCM), SCS and FLVQ on the IRIS dataset and see that it is more accurate due to its being able to take into account the covariance information. We finally note that vector quantization is generally an intermediate step before finding a final output for which supervision may be possible. Thus, instead of an uncoupled approach where an unsupervised method is used first to find the cluster parameters followed by supervised training of the mapping based on the memberships, we advocate a coupled approach where the cluster parameters and mapping are trained supervised in a coupled way. The uncoupled approach ignores the error at the outputs which may not be ideal.

Journal Article↗

Perceptual interference improves explicit memory but does not enhance data-driven processing.

Nairne (1988) has recently demonstrated that interfering with the perceptual processing of an item at study improves later memory for that item. Nairne hypothesized that interfering with perceptual processes induces a data-driven generation process that enhances the representation of visual information. Using a variant of Nairne's procedure, we both replicated his original findings and tested his hypothesis that enhanced data-driven processing causes the current effect. The results of studies using free recall and perceptual identification tests were inconsistent with Nairne's hypothesis. We consider several alternative interpretations in the General Discussion.

Adult↗