Autism and related conditions.
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Adrenal Cortex Hormones↗
Biomedical subjects
L Tsai
Publications and source records attributed to L Tsai.
Dietary exposures to selected metals and pesticides.
Average daily dietary exposures to 11 contaminants were estimated for approximately 120,000 U.S. adults by combining data on annual diet, as measured by a food frequency questionnaire, with contaminant residue data for table-ready foods that were collected as part of the annual U.S. Food and Drug Administration Total Diet Study. The contaminants included in the analysis were four heavy metals (arsenic, cadmium, lead, mercury), three organophosphate pesticides (chlorpyrifos, diazinon, malathion), and four organochlorine pesticides (dieldrin, p,p'-DDE, lindane, heptachlor epoxide). Dietary exposures to these contaminants were highly variable among individuals, spanning two to three orders of magnitude. Intraindividual exposures to the metals, organophosphates, and organochlorines were estimated to be strongly correlated; Pearson's correlation coefficients ranged from 0.28 for lindane:dieldrin to 0.84 for lead:mercury. For some of the compounds (e.g., arsenic and dieldrin), a substantial fraction of the population was estimated to have dietary intakes in excess of health-based standards established by the EPA. Before use for risk assessment or epidemiologic purposes, however, the validity of the exposure estimates must be evaluated by comparison with biological indicators of chronic exposure. Because of their low detection rate in table-ready foods, the estimated distributions of exposures for dieldrin, p,p'-DDE, heptachlor epoxide, lindane, diazinon, and chlorpyrifos were found to be sensitive to assumed values for nondetect samples. Reliable estimates of the population distribution of dietary exposures to most other contaminants cannot be made currently, due to their low rate of detection in table-ready foods. Monitoring programs that use more sensitive study designs and population-based assessments for other subpopulations should be a priority for future research.
Adult↗
Brief report: thought disorder in Asperger syndrome: comparison with high-functioning autism.
Asperger syndrome (AS) is a pervasive developmental disorder generally regarded as a variant of autism. While it has been included in the ICD-10 and DSM-IV as a distinct diagnostic entity, it is still unclear to what extent it differs from high-functioning autism (HFA). Persons with HFA have been reported to show a variety of deficits of thought processes. Abnormalities such as poor reality testing, perceptual distortions, and areas of cognitive slippage have been described using the Rorschach inkblot test (Dykens, Volkmar, & Glick, 1991). Since AS has been conceptualized as a mild variant of autism, we hypothesized that persons with AS will have fewer abnormalities on the Rorschach test compared to persons with HFA. To test this hypothesis, we compared 12 subjects with AS (ICD-10, 10 male, mean age = 12.2 +/- 3.3 years, mean full-scale IQ = 99.6) with 8 subjects with HFA (ICD-10/DSM-III-R, 7 male, mean age = 12.2 +/- 3.8 years, mean full-scale IQ = 83.4) on the Rorschach test. AS subjects demonstrated a trend towards greater levels of disorganized thinking than the HFA group. They were also more likely to be classified as "Introversive" suggesting that AS subjects may have more complex inner lives involving elaborate fantasies, Also, AS subjects tended to be more focused on their internal experiences. However, overall, the Rorschach test was not found to differentiate the two diagnostic groups on the majority of structural variables. Implications of these findings are discussed with regard to the diagnostic validity of Asperger syndrome.
Adolescent↗
The reaction of 4-hydroxy-2-nonenal with N alpha-acetyl-L-histidine.
The reaction of 4-hydroxy-2-nonenal and N alpha-acetyl-L-histidine was studied in pH 7.1 phosphate buffer. The main product isolated was assigned a cyclic hemiacetal structure formed by the addition of one of the imidazole nitrogen atoms to the alpha,beta-unsaturated aldehyde system of 4-hydroxy-2-nonenal. This structural assignment was based on the analyses of the NMR and mass spectral data of two derivatives obtained from the cyclic hemiacetal. The establishment of this cyclic hemiacetal structure supports the proposal made by Uchida and Stadtman6 that 4-hydroxy-2-nonenal modified histidyl residues in insulin by a Michael reaction.
Aldehydes↗
Obstetric factors in Asperger syndrome: comparison with high-functioning autism.
Asperger syndrome (AS) is a pervasive developmental disorder widely regarded as a mild variant of autism. To investigate if AS is associated with a history of fewer obstetric insults compared to autism, we examined the developmental history and obstetric records of 10 males with AS (mean full scale IQ 95.3), and compared them with 10 autistic males with a full scale IQ of 70 or above (so-called high-functioning autism; mean full scale IQ 82.6). Males with AS showed a trend toward lower Apgar scores at one minute (chi-square = 4; df = 1; P = 0.04) and were more likely to have been born to mothers outside the optimal age group of 20-30 years (chi-square = 5; df = 1; P = 0.02). They were also less likely to have been irritable and floppy as infants (chi-square = 3.8; df = 1; P = 0.05). However, the total optimality scores did not differ significantly between the two groups.
Adolescent↗
Strategy to detect and identify Bartonella species in routine clinical laboratory yields Bartonella henselae from human immunodeficiency virus-positive patient and unique Bartonella strain from his cat.
We wished to develop a cost-effective, rapid strategy to detect and identify Bartonella species in the clinical laboratory and to determine the prevalence of Bartonella infection in the Houston veteran population. Bartonella colonies were identified by colony morphology, Gram stain, RapID ANA, repetitive extragenic palindromic-PCR (REP-PCR) and whole-cell fatty acid (CFA) analysis, and these methods were compared for their usefulness. A new test order for "Rochalimaea culture" (the genus Bartonella was previously known as the genus Rochalimaea) was instituted, and in addition, all blood specimens submitted for fungal culture (obtained in an isolator tube) were processed for Bartonella culture. Over a 16-month period we isolated Bartonella henselae from only 0.4% (2 of 533) of total cultures but from 1% (2 of 204) of human immunodeficiency virus-positive patients. After sufficient growth, identification of the Bartonella isolates to the species level could be obtained in 2 days. The REP-PCR allowed discrimination of all known species, whereas CFA analysis distinguished all except B. henselae and Bartonella quintana. The RapID ANA results failed to differentiate between B. henselae and B. quintana, and results for other species differed by only one or two tests. Blood obtained from a kitten which had been introduced into the household of one patient 2 months before the onset of fever yielded a Bartonella strain which was shown to be different from the strain from the patient and distinct from other Bartonella species by a combination of REP-PCR, CFA, and growth characteristics. Subsequent analysis of the citrate synthase gene sequence showed only an 86% similarity with any of the other known Bartonella species, suggesting that this isolate represents a distinct, previously uncharacterized species of Bartonella.
AIDS-Related Opportunistic Infections↗
Cholesterol uptake by the 'selective' pathway of ovarian granulosa cells: early intracellular events.
Although the 'selective' pathway is a major cholesteryl ester (CE) uptake pathway used by steroidogenic cells, essentially nothing is known about the itinerary of the CE once it is extracted from lipoproteins at the cell surface. In the current report we have begun to trace 'selective' pathway internalized-CE using both native and reconstituted human (h) high density lipoproteins (hHDL3) with variously labeled and tagged CEs to provide information from either a biochemical or morphological perspective. It appears that the amount of hHDL3-CE that is internalized and processed through the 'selective' pathway is directly related to the amount of cholesterol used for steroidogenesis at any given time point. There is a time-related correlation between the level of the Bt2cAMP-stimulated cell steroidogenic response, the level of conversion of freshly obtained hHDL3-CE into progestins, increases in hHDL3-derived CE internalization, hHDL3-CE hydrolysis, re-esterification and/or storage. None of this processing takes place in non-stimulated (non-Bt2cAMP treated) cells which do not secrete progestins despite the availability of hHDL3 as a cholesterol source. The data suggest that the 'selective' pathway has a special role in steroidogenic cells-one of providing sufficient cholesterol to fuel the required production of steroid hormones.
Animals↗
Enhanced expression of granulosa cell low density lipoprotein receptor activity in response to in vitro culture conditions.
Previous studies have shown that the B/E (low density lipoprotein [LDL]) receptor pathway plays a minor role in cholesterol uptake in the intact rat ovary, but when granulosa cells are isolated and maintained in culture, the cells develop a fully functional B/E receptor system. In the current study we examined the development of the B/E receptor over time (96 h) in culture and compared its physiological function, expression of mRNA and protein levels, and morphological events to the upregulation induced in 24 h by hormone (human chorionic gonadotropin [hCG] or Bt2cAMP). With both protocols, increased progestin production occurs and is associated with elevated binding, uptake, and degradation of LDL in the medium although the impact of Bt2cAMP stimulation on all these measurements is several times that observed with time alone. Only the hormone-stimulated LDL receptor response was associated with an increase in receptor protein (Western blot) or mRNA levels (RNase protection assay). We conclude that unstimulated granulosa cells show posttranslational increases in B/E receptor activity with time in culture, but transcriptional changes in B/E receptor follow stimulation with trophic hormone or its second messenger, cAMP.
Animals↗
Mutations affecting the pattern of the PNS in Drosophila reveal novel aspects of neuronal development.
Through a systematic genetic screen, we have identified 55 mutations that affect the development of the PNS of Drosophila embryos. These mutations specify 13 novel and 5 previously characterized genes and define new phenotypes for 2 other known genes. Five classes of mutant phenotypes were identified in the screen: gain of neurons, loss of neurons, abnormal position of chordotonal neurons, aberrant neuronal trajectories, and abnormal morphology of neurons. Phenotypic analyses of mutations identified in this study revealed three novel aspects of PNS development. First, we have identified a novel gene that may be required to define glial versus neuronal cell identity. Second, our data indicate that neuronal migration plays an important role in pattern formation in the embryonic PNS. Third, we have identified mutations that cause a lack of sensory organs, but unlike mutations in proneural genes, do not affect the formation of sensory organ precursors. These genes may be required for key aspects of neuronal differentiation. Our studies suggest that approximately 70 essential genes are required for proper PNS development in Drosophila embryos.
Animals↗
Chronic recurrent multiple evanescent white dot syndrome.
PURPOSE: Multiple evanescent white dot syndrome (MEWDS) is usually unilateral, self-limited, and monophasic. The purpose of this study was to demonstrate that a chronic recurring form of the disease exists. METHODS: Three patients with otherwise typical MEWDS were observed for 4 to 5 years. Their ocular histories and physical findings were recorded. RESULTS: Multiple recurrences (5-7) involving both eyes were noted in each of the three patients. Classic clinical findings were seen, including granularity to the macula, white dots, and optic disc changes. Despite these recurrences, the patients still retained visual acuity of 20/20 in each eye. CONCLUSION: A chronic recurrent form of MEWDS exists. The cause of MEWDS remains unknown, and it is unclear why these patients demonstrated this atypical clinical course.
Adult↗
Is clumsiness a marker for Asperger syndrome?
Although Asperger syndrome (AS) has been included in the ICD-10 as a distinct category within the pervasive developmental disorders, it is still unclear to what extent it differs from normal-intelligence autism (high-functioning autism; HFA). Persons with AS are said to be particularly clumsy. To test the hypothesis that clumsiness can reliably distinguish AS from autism, the present authors compared 11 patients with AS (ICD-10; 10 males; mean age, 13.6 years; mean IQ, 98) with nine patients with HFA (ICD-10/DSM-III-R; eight males; mean age, 12.9 years; mean IQ, 84). Clumsiness was assessed by the Bruininks-Oseretsky test. Both groups showed problems with coordination and the distribution of standard scores was virtually identical. This suggests that motor clumsiness, as measured by tests of coordination, may not reliably distinguish AS from HFA. However, qualitative differences may occur between the two groups in the manner in which movements are performed. Further research with larger samples may elicit differences into the pattern of motor deficits that occur in autism and AS.
Adolescent↗
Effect of okadaic acid on utilization of lipoprotein-derived cholesteryl esters by rat steroidogenic cells.
This study examines various functional, biochemical, and structural changes in rat adrenocortical and ovarian granulosa cells that could account for the decline in lipoprotein-supported hormone production after cell treatment with the protein phosphatase inhibitor, okadaic acid. Although the steroidogenic pathway enzymes in these cells are not in themselves affected by okadaic acid, the intracellular transport of cholesterol to important cellular processing sites is defective. That is, okadaic acid does not interfere with the internalization of lipoprotein-derived cholesteryl esters, but the mitochondrial utilization of cholesterol obtained from intracellular cholesterol storage sites is 50% reduced as compared to control cells. Two-dimensional electrophoresis gels from okadaic acid-treated cells demonstrate a number of hyperphosphorylated proteins. Morphological examination of the affected cells reveal completely disrupted Golgi complexes with attendant structures, but otherwise the cells appear unchanged. The results suggest that some necessary sterol transport protein (or cofactor or associated membrane) is adversely phosphorylated by okadaic acid, and is rendered dysfunctional.
Animals↗
Spinal posture, sagittal mobility, and subjective rating of back problems in former female elite gymnasts.
This study analyzed posture, spinal sagittal mobility, and subjective back problems in former female elite gymnasts in comparison with matched control subjects. The former gymnasts had less thoracic kyphosis than the control subjects. No difference in thoracic range of motion was found. In the lumbar spine there was no difference as to either posture or sagittal motion. The former gymnasts did not report a higher frequency of current back problems. In the former gymnasts 27% had subjective back problems. In the control subjects the corresponding value was 38%. We did not find any correlation between posture or range of motion and subjective rating of back problems in either of the groups. In conclusion, former female elite gymnasts did not have more back problems than an age matched control group.
Adult↗
Oxidative refolding of insulin-like growth factor 1 yields two products of similar thermodynamic stability: a bifurcating protein-folding pathway.
Can one protein sequence encode two structures? Oxidative folding of human insulin-like growth factor 1 (IGF-1), a globular protein of 70 residues, is shown to yield two products of similar thermodynamic stability. This observation is of particular interest in light of the recent demonstration that two of the three disulfide bonds in native IGF-1 rearrange in the presence of dithiothreitol [Hober, S., et al. (1992) Biochemistry 31, 1749-1756]. Kinetics of the IGF-1 folding pathway were monitored by high-performance liquid chromatography (rp-HPLC). Disulfide-pairing schemes of intermediates and products were established by peptide mapping. Two disulfide isomers were obtained as products: one with native insulin-like pairing [6-48; 18-61; 47-52] (designated native IGF-1; 60% yield) and the other with alternative pairing [6-47; 18-61; 48-52] (designated IGF-swap; 40% yield). The predominant early intermediate contains the single disulfide 18-61, which is shared in common by the two products. Relative yields of native IGF-1 and IGF-swap are independent of protein concentration under dilute conditions. In the absence of an added thiol reagent, each isomer is stable indefinitely at neutral pH; in the presence of an added thiol reagent, the two isomers interconvert with an Arrhenius activation barrier of 12 kcal/mol. Interconversion does not require complete reduction and yields the same ratio of products as initial folding, demonstrating thermodynamic control. Spectroscopic studies using circular dichroism (CD), infrared spectroscopy (FTIR), two-dimensional 1H-NMR (2D-NMR), and photochemical dynamic nuclear polarization (photo-CIDNP) suggest that IGF-1 and IGF-swap adopt similar secondary structures but distinct tertiary folds. Implications of these observations for understanding the topology of protein-folding pathways are discussed.
Amino Acid Sequence↗
Role of native disulfide bonds in the structure and activity of insulin-like growth factor 1: genetic models of protein-folding intermediates.
Insulin and insulin-related proteins contain three motif-specific disulfide bonds. Here we examine the role of these disulfide bonds in the folding and function of one family member, human insulin-like growth factor 1 (IGF-1). Analogues containing pariwise Cys-->Ser or Cys-->Ala substitutions were expressed in Escherichia coli, purified, and analyzed with respect to receptor-binding, solution structure, and thermodynamic stability. An analogue lacking all three disulfide bonds (designated des-Cys-IGF-1) is inactive and unfolded. Introduction of the [18-61] disulfide bond, previously shown to occur in an early intermediate in oxidative refolding [Miller, J. A., Owers-Narhi, L., Hua, Q. X., Rosenfeld, R., Arakawa, T., Rohde, M., Prestrelski, S., Lauren, S., S. Stoney, K. S., Tsai, L., & Weiss, M. A. (1993) Biochemistry (preceding paper in this issue)], results in a compact partially folded state with low but significant biological activity. Additional but incomplete structural organization and biological activity are observed following introduction of either the [6-48] or the [47-52] disulfide bonds. Native function, structure, and stability require the presence of all three disulfide bonds. These analogues provide genetic models of IGF-1 protein-folding intermediates. Their characterization suggests that bifurcation of the IGF-1 folding pathway reflects alternative late steps in the folding of a molten-globule intermediate.
Amino Acid Sequence↗
Inactivation of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal. Selective modification of an active-site lysine.
Incubation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides with 4-hydroxy-2-nonenal (HNE) results in a pseudo first-order loss of enzyme activity. The pH dependence of the inactivation rate exhibits an inflection around pH 10, and the enzyme is protected from inactivation by glucose 6-phosphate. Loss of enzyme activity corresponds with the formation of one carbonyl function per enzyme subunit and the appearance of a lysine-HNE adduct. The data presented in this paper are consistent with the view that the epsilon-amino group of a lysine residue in the glucose 6-phosphate-binding site reacts with the double bond (C3) of HNE, resulting in the formation of a stable secondary amine derivative and loss of enzyme activity. We have described a mechanism by which HNE may, in part, mediate free radical damage. In addition, a method for the detection of the lysine-HNE adduct is introduced.
Aldehydes↗
Basal concentrations of anabolic and catabolic hormones in relation to endurance exercise after short-term changes in diet.
This study aimed to use a classical model to analyse whether alterations in performance due to short-term changes in diet are reflected in peripheral basal anabolic and catabolic hormone concentrations. Six healthy students (two women and four men) performed a cross-over study including three test situations. The reference test was preceded by each subject's normal unrestricted diet of western type (N). After this, three of the subject's were provided a carbohydrate-rich diet (CHO) for 3 days followed by the second test. Following this test, a carbohydrate deficient, protein/fat rich diet (F) was provided for another 3 days followed by the third test. The remaining three subjects had these diets in reverse order. Basal concentrations of cortisol (C), sex hormone-binding globulin (SHBG), insulin-like growth factor (IGF-I), total-testosterone and non-SHBG-bound-testosterone (NST), the NST:C ratio and an ergometer cycle endurance test with measurements of submaximal as well as measurements of maximal oxygen uptake, heart rate, respiratory exchange ratio (R), free fatty acids (FFA), glycerol and lactate were investigated. All the subjects were involved in athletics for recreation and during the study they performed daily physical exercise according to their normal routine. After the F diet only two of the subjects completed the test. One woman dropped out after 16 min, two men dropped out after 14 min and one after 13 min of cycling. After the CHO diet all six subjects completed the ergometer cycle test. Considering the whole group, there were no significant differences in lactate or glycerol concentrations during the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗