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PubMed2004

Lack of evidence for an association between WNT2 and RELN polymorphisms and autism.

Autism is a pervasive neurodevelopmental disorder characterized by deficits in language development and social interaction, as well as stereotypical, repetitive behaviors. The etiology of autism is largely unknown. Family and twin studies have provided compelling evidence for a strong genetic component in most idiopathic cases. Several recent candidate gene studies have suggested that alleles of WNT2 and the reelin gene (RELN), two genes involved in distinct aspects of neurodevelopment, confer greater susceptibility to autism. We screened WNT2 for DNA polymorphisms by sequencing all exons and adjacent intronic regions in 24 autistic patients, and identified not only the WNT2 variants reported previously (two common single-nucleotide polymorphisms (SNPs) in the 5' upstream region and the 3' untranslated region (UTR), respectively), but also two new SNPs in its 3' UTR. We genotyped all four WNT2 polymorphisms and a polymorphic trinucleotide repeat in the 5' UTR of RELN in 107 families with multiple autistic children, and evaluated evidence for association between these variants and autism by the transmission disequilibrium test (TDT). Our results revealed no deviation from the null hypothesis of no association. Our interpretation of these findings is that it is unlikely that DNA variations in RELN and WNT2 play a significant role in the genetic predisposition to autism.

5' Untranslated Regions↗

PubMed1992

A kinetic model for binding protein-mediated arabinose transport.

A kinetic model is presented based on the simplest plausible mechanism for bacterial binding protein-dependent transport. The transport phenotypes of the 18 variant arabinose-binding proteins analyzed by Kehres and Hogg (1992, Protein Sci. 1, 1652-1660) (wild type and 17 mutants) are interpreted to mean that in wild-type arabinose uptake the forward transport rate (k(for)) greatly exceeds the dissociation rate (kund) of a binding protein docked with the AraG:AraH membrane complex, and that k(for) dominance is preserved in all of the binding protein surface mutants. The assumptions and predictions of the model are consistent with existing data from other periplasmic transport systems.

Arabinose↗

PubMed1993

Individual-administered human behavioral test batteries to identify neurotoxic chemicals.

Most research demonstrating behavioral effects of occupational chemical exposures is produced in established laboratories using a consistent set or battery of tests. Exemplifying this tradition are batteries developed at Finland's Institute of Occupational Health, Milan's Institute of Occupational Health, Sweden's National Institute of Occupational Health, Australia's National Institute of Occupational Safety and Health, and at universities in the United States and other countries. In 1983, under the World Health Organization (WHO) aegis, experienced human occupational researchers recommended the Neurobehavioral Core Test Battery (NCTB) as a screening instrument to be administered by an individual to subjects exposed to chemicals believed to be neurotoxic. Health professionals from 50 cities in 27 countries distributed on every large continent have been trained to administer the NCTB according to its Operational Guide. Six issues need to be addressed regarding human-administered test batteries: (a) The critical role of individual-administered batteries to screen chemically exposed populations in a field increasingly dominated by computer-administered batteries; (b) selection criteria for tests to assess known and unknown chemicals; (c) utility of baseline data for study analysis and interpretation; (d) test battery validation; (e) availability and cost of inexpensive test batteries; and (f) equivalence of computer- and human-administered variants of the same tests.

Behavior↗

PubMed1998

Effect of diltiazem on sympathetic hyperactivity in patients with vasospastic angina as assessed by spectral analysis of arterial pressure and heart rate variability.

The autonomic nervous system importantly regulates coronary arterial tone and vascular resistance. To evaluate a role of autonomic nervous activity and the effects of calcium antagonist in patients with vasospastic angina (VSA), 13 VSA patients with patent coronary arteries (58+/-8 years) and 8 normal subjects (58+/-12 years) were studied. Arterial pressure and electrocardiogram were continuously recorded with the patient in a supine position under controlled respiration (0.2 Hz). Low-frequency (LF) and high-frequency (HF) components of the beat-to-beat variabilities of systolic arterial pressure and RR interval were then estimated by autoregressive power spectral analysis. The LF power (normalized unit) of both systolic arterial pressure (0.53+/-0.17 vs 0.30+/-0.17, p < 0.01) and RR variabilities (0.51+/-0.20 vs 0.31+/-0.16, p < 0.05) in patients with VSA were greater than that in normal subjects. There was no significant difference in the HF power. Seven patients with VSA who were treated with diltiazem (60 to 200 mg/day) had normalized LF power (normalized unit) of both systolic arterial pressure (0.62+/-0.12 vs 0.33+/-0.16, p < 0.01) and RR variabilities (0.55+/-0.23 vs 0.36+/-0.14, p < 0.05), together with clinical improvement. An increased sympathetic vasomotor tone and cardiac sympathetic predominance may play an important role in patients with VSA. Diltiazem improves these sympathetic hyperactivities.

Angina Pectoris, Variant↗

PubMed1997

Microevolution and epidemic spread of serogroup A Neisseria meningitidis--a review.

An extensive and representative strain collection of serogroup A Neisseria meningitidis was established. These bacteria were obtained from different endemic and epidemic/pandemic sources and include strains from diseased patients and healthy carriers. The genetic relationships of the bacteria were defined by multi-locus enzyme electrophoresis and sequence polymorphisms of genetically variable antigens have been analyzed in closely-related groupings. The results are interpreted as reflecting a balance of recombination events, which disrupt clonal relationships, and sequential bottlenecks, which purify the bacterial population of genetic variants during epidemic spread.

Alleles↗

PubMed2002

Benign liver neoplasms.

A variety of benign focal liver lesions are easily characterized with currently available imaging techniques and contrast agents. The most common benign liver lesions, such as hemangioma, bile duct cyst, and FNH, reveal characteristic cross-sectional imaging features that allow an accurate diagnosis. For atypical variants and more uncommon lesions, including HCA, angiomyelioma, infantile hemagioendothelioma, and mesenchymal hamartoma, integration of clinical data can often help in the interpretation of imaging studies. Finally, for the remaining lesions, such as hepatic adenomatosis, the imaging findings may not be specific enough to negate the need for a tissue biopsy.

Adenoma↗

PubMed2003

The application of the precautionary principle to the blood system: the Canadian blood system's vCJD donor deferral policy.

The precautionary principle is an influential concept that has been widely used in international treaties and declarations involving the protection of the environment. The principle is now being applied to the development of transfusion policy. In this article, we examine the application of the precautionary principle in the policy process leading to Canada's decision to defer donations from individuals who had traveled to the United Kingdom because of concerns over variant Creutzfeldt-Jakob disease. We found that, although the principle prominently influenced the decision-making process, problems existed with its interpretation. In particular, there was difficulty in balancing the risk prevented by applying a precautionary measure against the risk introduced by the same measure; in this case, the potential for shortages of blood. This dilemma is somewhat unique to the public health sector and will likely recur in future applications of the principle to transfusion policy.

Blood Banks↗

PubMed2005

[Ultrasound evaluation of the acromioclavicular joint. A comparison with magnetic resonance imaging].

INTRODUCTION: Ultrasound is useful in detecting acromioclavicular pathologies in cases of trauma, inflammations and degenerative changes in sports medicine. Many studies compare joint space and capsular dimensions of symptomatic and asymptomatic patients. However, no study has examined the reproducibility and reliability of these measurements. The aim of this study was to evaluate the reliability of ultrasonographic measurements in assessing the acromioclavicular joint. MATERIALS AND METHODS: 27 acromioclavicular joints of 15 healthy subjects were examined by T1 weighted magnetic resonance imaging (MRI) to determine the normal limits of joint space (a) and joint capsule (b). These measurements were compared to standardised ultrasonographic (11 Mhz) measurements, which were repeated three times. RESULTS: The mean difference between MRI and ultrasound measurements was 1.5 +/- 1.3 mm and 1.3 +/- 1.2 mm for distance a and b, respectively. Reproducibility of ultrasonographic measurements was high with a mean standard deviation of 0.3 +/- 0.2 mm and 0.4 +/- 0.3 mm for distance a and b, respectively. CONCLUSION: Due to low costs, safety and wide availability ultrasonography is suited for the evaluation of the acromiocalvicular joint. However, when interpreting the results measurement errors, limitations in resolution of the system used, and the anatomy of the acromioclavicular joint and its anatomic variants have to be taken into consideration.

Acromioclavicular Joint↗

PubMed1999

Altered substrate selectivity in a mutant of an intrahelical salt bridge in UhpT, the sugar phosphate carrier of Escherichia coli.

Site-directed and second site suppressor mutagenesis identify an intrahelical salt bridge in the eleventh transmembrane segment of UhpT, the sugar phosphate carrier of Escherichia coli. Glucose 6-phosphate (G6P) transport by UhpT is inactivated if cysteine replaces either Asp388 or Lys391 but not if both are replaced. This suggests that Asp388 and Lys391 are involved in an intrahelical salt bridge and that neither is required for normal UhpT function. This interpretation is strengthened by the finding that mutations at Lys391 (K391N, K391Q, and K391T) are recovered as revertants of the inactive D388C variant. Further work shows that although the D388C variant is null for G6P transport, movement of 32Pi by homologous Pi/Pi exchange is unaffected. This raises the possibility that this derivative may have latent function, a possibility confirmed by showing that D388C is a gain-of-function mutation in which phosphoenolpyruvate (PEP) is the preferred substrate. Added study of the Pi/Pi exchange shows that in wild type UhpT this partial reaction is readily blocked by G6P but not PEP. By contrast, in the D388C variant, Pi/Pi exchange is unaffected by G6P but is inhibited by both PEP and 3-phosphoglycerate. These latter substrates are used by PgtP, a related Pi-linked antiporter, which lacks the Asp388-Lys391 salt bridge but has instead an uncompensated arginine at position 391. For this reason, we conclude that in both UhpT and PgtP position 391 can serve as a determinant of substrate selectivity by acting as a receptor for the anionic carboxyl brought into the translocation pathway by PEP.

Amino Acid Sequence↗

PubMed2002

UK dietary exposure to BSE in head meat: by birth cohort and gender.

BACKGROUND: UK dietary exposure in 1980-1996 to the bovine spongiform encephalopathy (BSE) infectious agent through the consumption of beef mechanically recovered meat (MRM) contained in burgers, sausages and other meat products has already been quantified by birth cohort (born pre-1940, 1940-1969 or post-1969) and gender. In this paper, similar quantification is undertaken for the consumption of bovine head meat. METHODS: Synthesis of evidence on clinical BSE bovines, on bovines slaughtered in the last year of their BSE incubation period, brain contamination during head meat production, brain infectivity (option 1: 1-year preclinical bovine 54% as infectious as clinical BSE bovine; option 2: 1-year pre-clinical bovine as infectious as clinical BSE bovine) and 1980-1996 UK dietary consumption of head meat in burgers, sausages and other meat products. FINDINGS: Median infectivity consumed in head meat was 49 900 (67 800 for infectivity option 2), 96 200 (126 900) and 24950 (32 800) bovine oral (Bo) ID 50 units for the post-1969, 1940-1969 and pre-1940 birth cohorts in 1980-1989; and 143 950 (266 550 for infectivity option 2), 150 900 (279 500) and 38 350 (71 250) Bo ID50 units in 1990-1996. Males consumed almost 58% of infectivity in 1980-1996. For all three birth cohorts, exposure to BSE in head meat was higher in 1990-96 for both infectivity options. Median infectivity consumed in head meat and beef MRM was 83 150 (109 000 for infectivity option 2), 161 900 (207 450) and 39 300 (50 450) Bo ID50 units for the post-1969, 1940-1969 and pre-1940 birth cohorts in 1980-1989; and 188 200 (348 700), 190 600 (353 050) and 47 200 (87 550) Bo ID50 units in 1990-1996. INTERPRETATION: Males consumed almost 58% of BSE infectivity in head meat and beef MRM, which is consistent with 60 males of 113 variant Creutzfeldt-Jakeb disease (vCJD) onsets to 30 November 2001. If vCJD onsets to that date had all been infected in 1980-1989, 65 of 113 vCJD onsets in the post-1969 cohort are not consistent with its BSE exposure in 1980-1989 unless the vCJD incubation period or susceptibility depends on age, or another exposure is involved. Experimental data are needed to identify which brain material contaminates head meat, and further pathogenesis data are needed to determine the corresponding infectivity. Other salient sensitivity issues are highlighted.

Adult↗

PubMed1989

CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells.

An expression vector capable of encoding full-length CCAAT/enhancer-binding protein (C/EBP) has been constructed and tested in transient transfection assays for its capacity to activate transcription from the promoter of the serum albumin gene. When tested in cultured hepatoma cells, the C/EBP expression vector achieved potent trans-activation of the albumin promoter. Less substantial activation was observed when the same experiment was conducted using cultured mouse fibroblasts. Expression vectors that encoded defective forms of C/EBP failed to activate the albumin promoter. Moreover, mutated variants of the albumin promoter that lack the C/EBP-binding site failed to be trans-activated. The data are consistent with the interpretation that C/EBP is a bona fide transcription factor. During the course of these experiments it was noted also that C/EBP is more than an order of magnitude less concentrated in cultured hepatoma cells than it is in adult liver cells. Given these findings, we speculate that C/EBP may play a general role in establishing and maintaining the differentiated, nonproliferative state.

Animals↗

PubMed1975

Variants of Escherichia coli giving the appearance of mixed growths in urine.

Urines from patients with symptoms of urinary tract infection yielded mixed growths of different colony types of Escherichia coli. The different colony types were found to be variants of single infecting strains caused by mutation or by phase action. It is suggested that care should be exercised in the interpretation of apparently mixed growths from urine.

Bacteriophages↗

PubMed1980

Characterization of pepsin fragments of laminin in a tumor basement membrane. Evidence for the existence of related proteins.

Laminin was extracted with neutral buffer from a tumor basement membrane and subjected to extensive degradation by pepsin. The treatment released two homogenous fragments P1 (Mr = 290,000) and P2 (Mr = 45,000) in addition to a mixture of smaller peptides. Fragments P1 and P2 together contained more than 90% of the disulfide bonds and accounted for about one third of the mass of laminin. Both peptides differed in amino acid composition, immunological properties and a complex chain structure demonstrating the existence of two disulfide-bonded domains in the molecule. Part of the laminin in the tumor matrix could only be solubilized by pepsin treatment and several fragments were purified. The major fragment P1i closely resembled P1 of soluble laminin in its chemical and immunological properties. Minor fragments Pa, Pb, Pc and Pd (Mr = 44,000-74,000) were only related to P1 or P2 in amino acid composition, chain pattern and antigenicity. The data were interpreted as indicating that proteins similar but not identical to laminin exist in the basement membrane and account for the minor peptide variants.

Amino Acids↗

PubMed2006

In silico criterion for prediction of effects of p53 gene missense mutations on p53-Mdm2 feedback loop.

The Informational Spectrum Method (ISM) is the tool for the in silico analysis of proteins which interprets protein sequence linear information using signal analyses methods. In this paper the ISM was employed to characterize the products of genetic variants of tumor suppressor gene p53 and its natural binding regulator protein Mdm2. Based on this we propose the criterion for identification of missense mutations that have impact on the p53-Mdm2 feedback loop. The efficiency of the proposed criterion was confirmed by the ISM analyses of p53 mutants reported in: (i) healthy individuals, (ii) germline mutations database and (iii) somatic mutations database.

Amino Acid Sequence↗

PubMed1994

MR imaging of the breast in patients with silicone breast implants: normal postoperative variants and diagnostic pitfalls.

Because of the wide variety of types of silicone breast implants, modifications, and surgical procedures, a number of normal variants and potentially misleading appearances can be encountered on MR images of breast implants. Familiarity with these findings is essential to proper interpretation of these images. The purpose of this essay is to illustrate the overlap in appearances of MR images in different clinical scenarios. When confusing findings are present, confirmation of the surgical history can usually clarify the matter.

Adult↗

PubMedDate not supplied

Techniques for direct radiographic visualization during closed pinning of supracondylar humerus fractures in children.

After reduction of a displaced supracondylar humerus fracture, the distal humerus must be easy to visualize; radiographic techniques in which the forearm overlaps the distal humerus make interpretation of fracture reduction difficult. Eighteen patients with displaced supracondylar humerus fractures were treated with reduction that was maintained manually with a variant of Dunlop's extension traction. This allows direct fluoroscopic evaluation of Baumann's angle, the contour of the distal humerus, the pin insertion site, and the angle of pin insertion. In young patients with a thin distal humerus and swollen elbow, the easiest pin placement may be achieved by inserting the pin on the lateral view (after the anteroposterior view confirms a satisfactory reduction).

Child↗

PubMed1985

Analytical patterns and biochemical properties of macro creatine kinase type 2.

Here we describe our findings for 105 patients' sera containing macro creatine kinase (CK) type 2, as confirmed by exclusion chromatography. Depending on the technique used for determining isoenzyme CKs (electrophoresis, ion-exchange chromatography, immunoinhibition), this variant CK shows characteristic patterns and interferes in CK-MB assays by different mechanisms and to various degrees, thus complicating test interpretation. Macro CK type 2 evidently is not of cytoplasmic origin; rather it is a separate CK activity of human serum, characterized by its heat stability and, especially, by its increased molecular mass and high energy of activation. These latter characteristics have never been associated with the normal-size, dimeric cytoplasmic CK isoenzymes, but are typical for mitochondrial CK isolated from human tissues. We conclude that mitochondrial CK released after severe cell damage usually appears in blood in macromolecular forms (macro CK type 2), not in a dimeric form.

Chromatography, Gel↗

PubMed1996

The generation of antibody diversity in the turtle.

The Ab response in reptiles has been studied at the protein level, and in turtles some aspects resemble those of cold-blooded vertebrates from other classes. The genetic bases for these features are not clear. The present study is the first on the IgH organization and complexity of a reptilian Ig gene system. The approach to cloning turtle (Pseudemys scripta) sequences is entirely PCR based, and its efficacy is demonstrated by obtaining extensive information on a heretofore unexplored Ig gene system. A number of genomic VH sequences, representing possibly four families, were isolated, as was a genomic C mu 4 clone. These sequences, used as probes, provided proof that in the turtle there is a single IgH locus with multiple VH genes and one C mu gene. In Northern hybridizations, the C mu 4 probe detected two transcripts; of the four VH groups, only one was expressed, and multiple bands indicated the presence of at least two non-mu transcripts. Using reverse transcription-PCR on spleen or liver RNA, an IgM heavy chain sequence was obtained, as were a number of VDJ rearrangements. Among 32 unique VDJ rearrangements from one animal, there were 22 sequence variants at framework 4, suggesting either a very large number of J segments or somatic modification in the variable region. The latter interpretation is supported by point mutations found in framework 3 and CDR3. The number of changes is considerably greater than the deduced Taq misincorporation rate (0.05%).

Amino Acid Sequence↗