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Biomedical subjects

J Gould

Publications and source records attributed to J Gould.

At least 37 records · Page 2Linked to original sources

Are there subgroups within the autistic spectrum? A cluster analysis of a group of children with autistic spectrum disorders.

Comprehensive data on the developmental history and current behaviours of a large sample of high-functioning individuals with diagnoses of autism, Asperger's syndrome, or other related disorder were collected via parent interviews. This provided the basis for a taxonomic analysis to search for subgroups. Most participants also completed theory of mind tasks. Three clusters or subgroups were obtained; these differed on theory of mind performance and on verbal abilities. Although subgroups were identified which bore some relationship to clinical differentiation of autistic, Asperger syndrome, and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) cases, the nature of the differences between them appeared strongly related to ability variables. Examination of the kinds of behaviours that differentiated the groups suggested that a spectrum of autistic disorders on which children differ primarily in term of degrees of social and cognitive impairments could explain the findings.

Adolescent↗

Renal adenosine A1 receptor binding characteristics and mRNA levels during the development of acute renal failure in the rat.

1. The binding characteristics and mRNA levels for renal adenosine A1 receptors were investigated in normal rats and rats with acute renal failure (ARF) induced by either glycerol or HgCl2. 2. Saturation isotherms determined from the binding of [3H]-1,3-dipropyl-8-cyclopentylxanthine ([3H]-DPCPX), a selective adenosine A1 antagonist, to renal membranes of untreated rats gave values of 0.62 nM for the equilibrium dissociation constant (Kd) and 19.9 fmol mg-1 protein for the density of binding sites (Bmax). No saturable binding was observed with [3H]-2-(p-(carboxylethyl)-phenylethylamino)-5'-N-ethylcar box amido adenosine ([3H]-CGS 21680), a selective adenosine A2a agonist. 3. By contrast to time-matched controls, renal membranes obtained from rats 16 and 48 h following the induction of ARF with glycerol, showed statistically significant increases (2-4 fold) in both Bmax and Kd for the binding of [3H]-DPCPX. No significant changes in the binding characteristics of [3H]-DPCPX were noted with membranes from rats 48 h following the production of ARF with HgCl2. 4. Adenosine A1 receptor mRNA levels were significantly elevated 0.5, 16 and 48 h following induction of ARF with glycerol, whilst no change was noted in mRNA levels for beta-actin at the same time points. No statistically significant changes in adenosine A1 receptor or beta-actin mRNA levels were noted 48 h after the induction of ARF with HgCl2. 5. This study indicates that glycerol-induced ARF in the rat is associated with an increase in renal adenosine A1 receptor density which appears to result from increased transcription of the gene for this receptor. An increase in adenosine A1 receptor density in renal resistance vessels may explain, at least in part, the enhanced renal vasoconstrictor response to adenosine in glycerol-induced ARF that was noted in a previous study.

Acute Kidney Injury↗

Regulation of Pdha-2 expression is mediated by proximal promoter sequences and CpG methylation.

Spermatogenesis is a complex process requiring the coordinate expression of a number of testis-specific genes. One of these, Pdha-2, codes for the murine spermatogenesis-specific isoform of the E1a subunit of the pyruvate dehydrogenase complex. To begin to delineate the mechanisms regulating its expression in vivo, we have generated transgenic mice lines carrying Pdha-2 promoter deletion constructs. Here we report that transgenic mice harboring a construct containing only 187 bp of promoter and upstream sequences (core promoter) is sufficient for directing the testis-specific expression of a chloramphenicol acetyltransferase (CAT) reporter gene. Like the endogenous Pdha-2, the CAT gene is expressed in testis in a stage-specific manner. Our studies also show a correlation between CpG methylation within the core promoter and its capacity to regulate transcription. In NIH 3T3 cell lines stably transfected with the Pdha-2 core promoter-CAT construct, high levels of CAT reporter expression are observed, whereas the endogenous Pdha-2 gene is repressed. In these cells, the CpG dinucleotides residing within the transfected promoter are hypomethylated whereas those residing in the endogenous promoter are methylated. Furthermore, promoter activity can be abated by the in vitro methylation of its CpG dinucleotides. DNase I footprint analysis indicates that at least one site for the methylation-mediated repression may occur through the ATF/cyclic AMP response element binding element located within the core promoter. Mutations within this element reduces activity to approximately 50% of the wild-type promoter activity. These results suggest that tissue-specific gene expression may be modulated by other mechanisms in addition to specific transcription factor availability and cooperativity. We propose that methylation may be a mechanism by which repression of the testis-specific Pdha-2 gene is established in somatic tissue.

3T3 Cells↗

Comparison of clinical symptoms in autism and Asperger's disorder.

OBJECTIVE: To determine what clinical symptoms clinicians have been using to distinguish between Asperger's disorder (AsD) and autistic disorder (AD). METHOD: Parents of children and adolescents with high-functioning AD (n = 48) and AsD (n = 69) were given a structured interview based on DSM-III-R and ICD-10 diagnostic criteria. Information regarding early and current symptom presentation and family, developmental, and verbal mental age information were collected. Logistic regression analyses were conducted to determine which variables best predicted clinician's diagnosis. RESULTS: A number of clinical variables predicted diagnosis. Delayed language onset was the only variable of the family and developmental variables that predicted diagnosis. The AsD group was also significantly higher than the AD group in verbal mental age. CONCLUSION: Clinicians appear to be diagnosing AsD and AD on the basis of published research and case study accounts. The findings question whether DSM-IV and ICD-10 criteria adequately describe the AsD individual, particularly in the communication domain.

Adolescent↗

The response of injection drug users to free treatment on demand: implications for HIV control.

Injection drug use is a major risk factor for human immunodeficiency virus (HIV) infection and drug treatment is widely recognized as a core component of the public health effort to limit the spread of HIV. The assumption is frequently made that lack of immediate access to treatment is a significant barrier to the success of this effort. However, little empirical data exist to support this belief. We conducted a trial of no-cost outpatient drug-free treatment made available on demand to a cohort of out-of-treatment injection drug users (IDUs) in Portland, Oregon, through a coupon program. Of 824 IDUs, 272 (33%) expressed an interest in treatment, 225 (27%) accepted a coupon, 66 (8%) redeemed a coupon, and 9 (1%) remained in treatment for 6 months. These numbers indicate that simply enhancing access is not adequate. Additional strategies to increase motivation to enter and remain in treatment are needed if drug treatment is to play an important role in reducing the spread of HIV among injection drug users, their sexual partners, and their infants.

Adolescent↗

Maternal risks for very low birth weight infant mortality.

OBJECTIVE: To determine whether known maternal risk factors for low birth weight directly contribute to infant mortality among very low birth weight infants. DESIGN: Retrospective population-based, case-control study. SETTING: Four hospitals in the Oakland, California, area: one community, two private, one health maintenance organization. PARTICIPANTS: All live-born singleton very low birth weight ( < 1500 g) infants born to Oakland residents over a 3-year period. Cases were infants who died before their first birthday, identified by computerized linkage of birth and death certificates. For each case, a surviving control was selected to match for birth weight, sex, and race. Forty matched pairs were identified in total. OUTCOME MEASURES: Prevalence of maternal risk factors among cases versus controls. RESULTS: After controlling for other factors known to influence either birth weight or infant mortality, maternal cocaine use (odds ratio [OR] = 5.43), prior infant death (OR = 27.14), and planned pregnancy (OR = 6.33) were significantly associated with the survival of very low birth weight infants. CONCLUSIONS: Some maternal risk factors for low birth weight confer a survival advantage to very low birth weight infants. Our data reveal that maternal cocaine use is independently associated with survival among this subset of infants. Prior research supports the observed relationship as well as the scientific plausibility of a cocaine-mediated survival advantage among premature infants. Our study also showed both planned pregnancy and prior infant death to be independently associated with infant survival among this subset of infants, suggesting that maternal behaviors may play a role in determining birth weight-specific mortality. These data should be systematically evaluated to better define their relationship to infant mortality.

Adolescent↗

Angiogenic activity of anterior pituitary tissue and growth hormone on the chick embryo chorio-allantoic membrane: a novel action of GH.

A useful system to evaluate the angiogenic activity of hormones and growth factors is the chorioallantoic membrane (CAM) of chick embryos. The present studies examined the angiogenic activity of chicken anterior pituitary glands and both fibroblast growth factor (FGF) and growth hormone (GH). Grafts of anterior pituitary gland evoked an angiogenic response on the CAM which was lost if the adenohypophyseal tissue was first boiled. The magnitude of the angiogenic response to anterior pituitary glands increased with the age of the donor (from a minimum 15 days of embryonic development to a maximum between 2 and 6 weeks old). In view of the similarity of the profile of the angiogenic response and the reported changes in GH secretion, the angiogenic activity of GH was then examined. Considerable angiogenic responses were observed with GH; there being increases (P < 0.05) in number of new blood vessels on the CAM of chick embryos on which native chicken GH or native bovine GH or recombinant bovine GH were added. These data support GH having an angiogenic action.

Allantois↗

Predicting symptomatology and self-blame among child sex abuse victims.

Fifty-six sexually-abused girls and their nonoffending female caretakers from primarily low-income. African American families were comprehensively assessed in order to determine factors related to child symptomatology and self-blame. Girls whose overall relationships with their caretakers were somewhat negative exhibited more behavioral difficulties. Girls with disruptions in their relationship with a primary caretaker and who felt powerless as a result of the abuse were rated as functioning less well overall by clinicians. Child age, general attributional style, and caretaker blame of the child were related to child self-blame. Clinical implications of these findings include identification of clients at high risk for negative sequelae and development of interventions targeted at specific clinical issues.

Adaptation, Psychological↗

The recognition of autism in children with Down syndrome--implications for intervention and some speculations about pathology.

Although autism can occur in conjunction with a range of other conditions, the association with Down syndrome is generally considered to be relatively rare. Four young boys with Down syndrome are described who were also autistic. All children clearly fulfilled the diagnostic criteria for autism required by the ICD-10 or DSM-III-R, but in each case the parents had faced considerable difficulties in obtaining this diagnosis. Instead, the children's problems had been attributed to their cognitive delays, despite the fact that their behaviour and general progress differed from other children with Down syndrome in many important aspects. The implications, for both families and children, of the failure to diagnose autism when it co-occurs with other conditions such as Down syndrome are discussed. Some speculations about possible pathological associations are also presented.

Age Factors↗

Renal haemodynamic responses to adenosine in acute renal failure.

Renal vascular reactivity was studied in rats with acute renal failure (ARF) to investigate whether changes in sensitivity to the renal haemodynamic effects of adenosine can explain why adenosine plays a significant role in some but not all forms of ARF. Experiments involved rats with glycerol-induced ARF in which adenosine antagonists have been shown previously to have beneficial effects and rats with HgCl2-induced ARF which was not ameliorated by treatment with the selective A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.1 mg/kg). Close renal arterial injections of adenosine (0.1-10 micrograms) or noradrenaline (0.003-0.1 microgram) produced falls in renal blood flow in rats with HgCl2-induced ARF which were not statistically different from controls. Adenosine evoked falls in renal blood flow in rats with glycerol-induced ARF which were significantly greater 16 and 48 h, but not 30 min after glycerol injection. The enhanced responsiveness to adenosine's renal constrictor effects was most pronounced 48 h following glycerol injection when, for example, a dose of 10 micrograms produced a fall of 60 +/- (SEM) 5% (n = 8) in renal blood flow in comparison to a fall of 27 +/- 5% (n = 8) in controls. By contrast to the renal vascular response to adenosine, the falls in renal blood flow induced by noradrenaline in rats 48 h following glycerol injection were not statistically different from the decreases in renal blood flow recorded in control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Self-help groups: a key to HIV risk reduction for high-risk injection drug users?

While recent studies indicate that injection drug users (IDUs) can change their behavior to reduce injection risk of HIV, it remains unclear which users are most likely to change and which mediating variables are most amenable to intervention. We report a study in which a cohort of high-risk IDUs was followed over time to determine which variables were associated with reduced injection risk of HIV. Of 317 IDUs who at baseline had shared a dirty needle in the previous 30 days, 234 (74%) were followed for 6 months. Of these, 107 (46%) reported reduced or eliminated injection risk between the baseline and follow-up interviews, 82 (35%) by not injecting and 25 (11%) by not sharing syringes. Those who attended self-help meetings between the two interviews were almost twice as likely to report reduced or eliminated risk as those who did not attend (OR = 1.92; p = 0.04). The findings suggest that, at least, IDUs in self-help groups comprise a population amenable to HIV interventions and, at most, that self-help groups may play an important role in reducing the risk of HIV in out-of-treatment populations.

Adult↗

Phase II study of intravenous idarubicin in unfavorable non-Hodgkin's lymphoma.

Idarubicin, a new analogue of daunorubicin, was administered intravenously at a dose of 15 mg/m2 to 31 patients with previously treated patients with unfavorable non-Hodgkin's lymphoma. Clinical characteristics included median age 69 years, performance status 1, and prior chemotherapeutic regimens 1. Twenty of the patients were relapsing after prior therapy and 11 were refractory; 29 had received prior anthracycline or anthracenedione. Responses were observed in 43% of patient (3 CR and 10 PR) with a median duration of 10+ months (2-29+ months). Idarubicin was well tolerated with non-hematologic toxicities (nausea/vomiting, mucositis, and anorexia) seen in < 50% of patients. Median hematologic values during the first cycle for this dosage included WBC 1300/mm3, platelets 129,000/mm3, and hemoglobin 10.9 mg/dl. With dose escalation, hematologic toxicity was dose-limiting. Symptomatic cardiac toxicity was observed in one patient who had received maximum dose doxorubicin and radiotherapy. Median values for the cardiac ejection fraction during the full course of therapy for the entire group of patients were 0.62 (initial) and 0.60 (final). Idarubicin in intravenous form is an active drug in previously treated patients with unfavorable non-Hodgkin's lymphoma. Further studies employing idarubicin in non-Hodgkin's lymphoma should be considered. Cardiac function should be followed in trials utilizing anthracycline-type chemotherapeutic agents.

Adult↗