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S Schwartz

Publications and source records attributed to S Schwartz.

At least 181 records · Page 10Linked to original sources
PubMed1998

The role of values in the nature/nurture debate about psychiatric disorders.

This paper discusses the role that values play in our estimates of the relative importance of nature/nurture factors in the etiology of psychiatric disorders. It is argued that all parameter estimates, heritability estimates, variance explained, odds ratios, and relative risks, are based, at least in part, on value judgements that are made in the course of our research activities. Four aspects of causal inference where values are particularly influential are discussed: gene/environment interactions, environmental specificity, the distinction between causes of variation and the causes of a factor, and the reification of our measures. The value component in our research is illustrated in two areas of research: life events and depression and individual factors in violence.

Environment↗
PubMed1998

Cryptococcosis in Hodgkin's disease: description of two cases and review of the literature.

Systemic mycosis caused by Cryptococcus neoformans frequently becomes life threatening in patients with cellular immunodeficiencies. In contrast to AIDS patients, there are only a few reports of concurrent systemic cryptococcosis in patients with Hodgkin's disease (HD). Only two of 75 (2.7%) patients with HD who were consecutively admitted to our hospital in the past decade developed Cryptococcus neoformans infection. Both had stage IVB (Ann Arbor) HD with bone marrow involvement and absolute lymphopenia (< 1/nl). We have reviewed the literature and analyzed the data of 54 cases with concurrent cryptococcosis and HD. Presence of HD for > or = 12 months, stage IV disease, absolute lymphopenia (< 1/nl), and extensive pretreatment were the most common features among these patients and must be regarded as predisposing for acquiring a cryptococcal infection. In our patients antimycotic therapy was successful using liposomal amphotericin B (lipAmB) simultaneously with cytotoxic therapy for HD. Drug level measurements performed in one patient revealed a higher level of amphotericin B in CSF when the liposomal formulation was administered as compared with the level in CSF after administration of conventional amphotericin B. To our knowledge, this is the first report on antimycotic treatment of cryptococcosis with lipAmB in patients with HD. Regarding the favorable therapeutic index of lipAmB as compared with conventional amphotericin B, the drug should be considered as a less toxic and perhaps more effective alternative in the therapy of acute cryptococcosis, especially when cytotoxic treatment is administered simultaneously.

Adult↗
PubMed1998

Reduced infectivity of human immunodeficiency virus type 1 produced in the presence of a truncated Gag protein containing p7 gag and p6 gag.

The C-terminal portion of human immunodeficiency virus type 1 p55gag protein, p15gag, contains two functional proteins; p6gag which is required for incorporation of Vpr into the virion, and p7gag which binds to viral RNA and is necessary for packaging of genomic RNA into virions. p7gag protein overexpressed in trans may compete with wild type p55gag for binding to genomic viral RNA, thereby inhibiting incorporation of RNA into the virions. To investigate if overexpression of the C-terminal portion of p55gag could interfere with generation of infectious virus, a plasmid producing a protein consisting of p2gag, p7gag and p6gag, termed p15gag*, was generated and cotransfected with an infectious proviral human immunodeficiency virus type 1 clone. Cells overexpressing p15gag* in trans produced approximately 40 fold less infectious virus than cells lacking exogenous p15gag*. These results demonstrated that expression of the C-terminal portion of p55gag efficiently reduced virus infectivity.

Base Sequence↗
PubMed1998

Oxidative stress induces age-dependent changes in lymphocyte protein synthesis and second messenger levels.

Cumulative damage in cells from aged people could lead to a greater fragility against acute oxidative stress. The effects of acute oxidative stress on cell viability, cAMP and cGMP concentrations, and protein synthesis rates were studied in lymphocytes from 25 young and 26 elderly subjects. Lymphocytes were exposed to stress by hydrogen peroxide 25 micromol/l and incubated for 18 hours. Cell viability after stress was lower (p<0.0001, Student's t test) in cells from the elderly (63.4%) than in cells from the young donors (73.2%). The protein synthesis rate was also lower after stress (p<0.04, Mann-Whitney U test) in cells from the elderly (47.3% vs. non-stressed cells), than in cells from the young (82.19% vs. non-stressed cells). After oxidative stress, cAMP and cGMP concentrations showed no significant changes in cells from young subjects; there were, however, significant decreases in these cyclic nucleotides in cells from the elderly (p<0.008 for both nucleotides, paired Student's t test). There were no differences in basal cAMP or cGMP levels between the two groups. These results show that mortality and metabolic changes due to oxidative stress are greater in lymphocytes proceeding from elderly subjects than in those from young subjects.

Adult↗
PubMed1998

Characterisation and partial purification of cellular factors interacting with a negative element on human papillomavirus type 1 late mRNAs.

We have previously identified and characterized an AU-rich inhibitory RNA element located in the 3' untranslated region on late human papillomavirus type 1 (HPV-1) mRNAs. This sequence is active in the absence of virus proteins and interacts specifically with cellular proteins, which presumably mediate the inhibitory activity. Here we have characterized and partially purified five proteins (80-, 52-, 46-, 44-, and 38-kDa) that interact independently and specifically with an AU-rich inhibitory sequence on HPV-1 late mRNAs. Dephosphorylation of the proteins resulted in loss of RNA binding activity. Proteins similar to the 38-, 44-, and 46-kDa proteins were detected also in murine epithelial cells, whereas proteins corresponding to the 80- and 52-kDa proteins were not. Since the inhibitory HPV-1 sequence is active in murine epithelial cells, the results suggested a role for the 38-, 41, and the 46-kDa proteins in the regulation of HPV-1 late gene expression.

Animals↗
PubMed1998

High rate of chromosome abnormalities detected by fluorescence in situ hybridization using BCR and ABL probes in adult acute lymphoblastic leukemia.

The value of dual-color fluorescence in situ hybridization (FISH) with BCR and ABL probes for the detection of the Philadelphia (Ph) translocation and of other alterations involving ABL and/or BCR was evaluated in adult acute lymphoblastic leukemia (ALL). One hundred and four patients were studied prospectively using interphase nuclei FISH, chromosome analysis (CA), and PCR assays for the chimeric BRC/ABL transcript. FISH detected a Ph translocation in 24 cases (23.1%), as was confirmed by CA and/or PCR. FISH revealed a false positive diagnosis of a Ph translocation in four cases (5% false positive rate). Among 54 cases with combined FISH, CA and PCR assays, FISH failed to establish a correct diagnosis in 3.7%, PCR in 5.6%, and CA in 7.4%. The combination of two screening methods led to discrepant results in 9.3% (FISH + PCR), 11.1% (FISH + CA), or 13% (CA + PCR) of the cases. In seven of 80 (8.8%) Ph-negative patients, gain of BCR and/or ABL was identified. Overall, FISH detected alterations of the BCR and/or ABL genes with an incidence of 29.8% of the current study. Due to the possibility of false positive diagnosis of a Ph translocation using dual-color FISH the combination with chromosome and/or RT-PCR analyses is recommended in adult ALL patients.

Adolescent↗
PubMed1998

Effect of oxidative stress on lymphocytes from elderly subjects.

1. Oxidative damage has been associated with ageing, but there is no agreement as to whether or not it is produced by a decrease in antioxidant defences with the ageing process. In purified lymphocytes from 47 healthy elderly (75.27 +/- 0.91 years) and 47 healthy young (29.87 +/- 0.53 years) volunteers, we studied the levels of antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase), protein oxidative damage (as protein carbonyl content) and lysosomal proteolytic activity (cathepsins B, H and L), with and without exposure to oxidative stress produced by 25 mumol/l H2O2. 2. There were no differences in antioxidant enzyme activities in the stressed and non-stressed samples between the young and elderly subjects, indicating that there was no relationship between age and antioxidant enzyme activity even in oxidative stress. However, a dissimilar response to oxidative stress was observed in protein oxidative damage and cathepsin B and L activities, depending on the age of the donor. 3. With these results we conclude that oxidative stress produces greater protein oxidative damage and increased protein degradation in elderly subjects than in young ones; this effect cannot be attributed to dissimilar antioxidant enzyme responses to oxidative stress, since these did not differ between the two age groups.

Adult↗
PubMed1998

Molecular cytogenetic evidence for a common breakpoint in the largest inverted duplications of chromosome 15.

Chromosomes from 20 patients were used to delineate the breakpoints of inverted duplications of chromosome 15 (inv dup[15]) that include the Prader-Willi syndrome/Angelman syndrome (PWS/AS) chromosomal region (15q11-q13). YAC and cosmid clones from 15q11-q14 were used for FISH analysis, to detect the presence or absence of material on each inv dup(15). We describe two types of inv dup(15): those that break between D15S12 and D15S24, near the distal boundary of the PWS/AS chromosomal region, and those that share a breakpoint immediately proximal to D15S1010. Among the latter group, no breakpoint heterogeneity could be detected with the available probes, and one YAC (810f11) showed a reduced signal on each inv dup(15), compared with that on normal chromosomes 15. The lack of breakpoint heterogeneity may be the result of a U-type exchange involving particular sequences on either homologous chromosomes or sister chromatids. Parent-of-origin studies revealed that, in all the cases analyzed, the inv dup(15) was maternal in origin.

Adolescent↗
PubMed1998

Evidence for a Turner syndrome locus or loci at Xp11.2-p22.1.

Turner syndrome is the complex human phenotype associated with complete or partial monosomy X. Principle features of Turner syndrome include short stature, ovarian failure, and a variety of other anatomic and physiological abnormalities, such as webbed neck, lymphedema, cardiovascular and renal anomalies, hypertension, and autoimmune thyroid disease. We studied 28 apparently nonmosaic subjects with partial deletions of Xp, in order to map loci responsible for various components of the Turner syndrome phenotype. Subjects were carefully evaluated for the presence or absence of Turner syndrome features, and their deletions were mapped by FISH with a panel of Xp markers. Using a statistical method to examine genotype/phenotype correlations, we mapped one or more Turner syndrome traits to a critical region in Xp11.2-p22.1. These traits included short stature, ovarian failure, high-arched palate, and autoimmune thyroid disease. The results are useful for genetic counseling of individuals with partial monosomy X. Study of additional subjects should refine the localization of Turner syndrome loci and provide a rational basis for exploration of candidate genes.

Adolescent↗
PubMed1998

Is juvenile obsessive-compulsive disorder a developmental subtype of the disorder? A review of the pediatric literature.

OBJECTIVE: To examine the clinical correlates of obsessive-compulsive disorder (OCD) in children and adolescents. METHOD: A systematic review of the extant literature on juvenile OCD was conducted examining age at onset, gender distribution, symptom phenomenology, psychiatric comorbidity, neurological and perinatal history, family psychiatric history, cognitive and neuropsychological profiles, and treatment and outcome in juvenile OCD subjects. RESULTS: Juvenile OCD was associated with a unique peak of age at onset indicating a bimodal incidence of the disorder, male preponderance, a distinct pattern of comorbidity with attention-deficit/hyperactivity disorder and other developmental disorders as well as frequent associated neuropsychological deficits, an increased familial loading for OCD, and frequent absence of insight. CONCLUSION: These findings show that juvenile OCD is associated with a unique set of correlates that appear to differ from findings reported in studies of adult OCD subjects. Although in need of confirmation, these findings suggest that juvenile OCD may be a developmental subtype of the disorder. Since juvenile OCD is likely to continue into adulthood, these findings stress the importance of considering age at onset in clinical and research studies of adults with OCD.

Adolescent↗
PubMed1998

Prader-Willi and Angelman syndromes. Disorders of genomic imprinting.

Prader-Willi and Angelman syndromes are 2 clinically distinct disorders associated with multiple anomalies and mental retardation. They are only discussed together because they share a similar and uncommon genetic basis: they involve genes that are located in the same region in the genome and are characterized by genetic imprinting. This normal process has contributed to these 2 complex and severe conditions through inactivation of 1 copy of the genes relevant to each disorder: the maternally derived copy of genes for Prader-Willi syndrome in proximal 15q are normally silent, and a paternally derived copy of 1 gene for Angelman syndrome in 15q is normally silent. For both disorders, when the normally active copy of the gene or genes is missing, abnormality results. Since the genes for these 2 disorders are located very close together, and since the center involved in inactivating the genes involved in imprinting may be the same, both these disorders usually result from the same chromosomal deletion; which disorder results depends on the parent of origin of the chromosome 15 that becomes deleted. Both Prader-Willi and Angelman syndrome can also occur as a result of having both members of the chromosome 15 pair derived from 1 parent, a condition known as uniparental disomy. Both can also result from a structural abnormality of the imprinting center, known as an imprinting mutation. In addition, Angelman syndrome can be caused by a mutation in the gene that causes it; a comparable cause is not present in Prader-Willi syndrome since it results from abnormality in more than 1 gene. Finally, despite the complexity of possible causes, all but the single gene mutation of the Angelman syndrome gene can be detected through methylation-sensitive DNA probes, since DNA methylation is the process by which the genes for these 2 disorders are imprinted. This unusual property of specific areas of the DNA holds promise for future treatment of these and other disorders related to imprinting through reversal of the imprinting process.

Adult↗
PubMed1998

The structure and dynamics of worry: theory, measurement, and cross-national replications.

This article presents a comprehensive conceptualization of the structure of worry and the relation of worry to mental health and well-being. It is assumed that worries have two facets, namely, the object of a worry (e.g., self, close others, society, the world) and the domain of a worry (the field of life with which it is concerned). The object of a worry is presumed to be more important than its domain in determining the impact of worries on mental health. Only worries concerned with self and close others (micro worries) are expected to be related to poor mental health, whereas worries about society or the entire world (macro worries) are expected to be positively related to mental health. An instrument is introduced to study worries in accordance with the proposed structure. Its validity is tested by two confirmatory techniques (similarity structure analysis and confirmatory factor analysis) in samples from Israel, West Germany, and (the former) East Germany. Worry scores are also related to five mental health indicators. Results show that across samples micro and macro worries can validly be distinguished. Micro worries are strongly related to poor mental health, whereas macro worries are unrelated to mental health or relate marginally to positive well-being.

Adaptation, Psychological↗
PubMed1998

Continuous unilateral epileptiform discharge and language delay: effect of functional hemispherectomy on language acquisition.

PURPOSE: To assess the efficacy of functional hemispherectomy in promoting language acquisition in a child with severe language delay and continuous left hemispheric epileptiform discharge in the absence of clinical seizures. We report a 6-month-old girl who initially presented with a right hemiparesis secondary to a lesion of probable prenatal origin in the distribution of the left middle cerebral artery. Weeks later, she developed infantile spasms. At 1.5 years of age, because of intractable seizures, the patient had fenestration of the left porencephalic cyst and anterior temporal lobectomy. The seizures ceased; however, language development remained limited to 35 words at 3.5 years of age. The EEG showed almost continuous epileptiform activity over the left hemisphere with no independent epileptiform potentials contralaterally. She underwent a functional left hemispherectomy. METHODS: Imaging, electroencephalographic investigation, pre- and postoperative psychological and speech assessment were carried out. RESULTS: Considerable language, speech, and behavior improvement was noted within 2 months of surgery. CONCLUSIONS: Interictal epileptiform discharges can interfere with the development of contralateral hemispheric function in the absence of clinical seizures. Early functional hemispherectomy may have a role in promoting optimal language development in appropriately selected patients. Although the primary indication for functional hemispherectomy is to control intractable seizures, a secondary proposed indication is to reduce functional impairment of the other hemisphere by electrical interference.

Brain↗
PubMed1998

mRNA instability elements in the human papillomavirus type 16 L2 coding region.

Human papillomavirus capsid proteins L1 and L2 are detected only in terminally differentiated cells, indicating that expression of the L1 and L2 genes is blocked in dividing cells. The results presented here establish that the human papillomavirus type 16 L2 coding region contains cis-acting inhibitory sequences. When placed downstream of a reporter gene, the human papillomavirus type 16 L2 sequence reduced both mRNA and protein levels in an orientation-dependent manner. Deletion analysis revealed that the L2 sequence contains two cis-acting inhibitory RNA regions. We identified an inhibitory region in the 5'-most 845 nucleotides of L2 that acted by reducing cytoplasmic mRNA stability and a second, weaker inhibitory region in the 3' end of L2. In contrast, human papillomavirus type 1 L1 and L2 genes did not encode strong inhibitory sequences. This result is consistent with observations of high virus production in human papillomavirus type 1-infected tissue, whereas only low levels of human papillomavirus type 16 virions are detectable in infected epithelium. The presence of inhibitory sequences in the L1 and L2 mRNAs may aid the virus in avoiding the host immunosurveillance and in establishing persistent infections.

Capsid↗
PubMed1998

Familial multiple symmetric lipomatosis associated with the A8344G mutation of mitochondrial DNA.

We describe familial multiple symmetric lipomatosis in a pedigree harboring the 8344 mutation in the tRNA(Lys) gene of mitochondrial DNA (mtDNA). The proband showed neuromuscular involvement but lacked the typical manifestations of myoclonic epilepsy and ragged-red fibers disease. The distribution of the mutation was unusual because the proportion of mutated genomes was higher in blood and lipomas than in muscle tissue.

Adult↗
PubMed1998

Molecular genetic analysis of McArdle's disease in Spanish patients.

We analyzed leukocyte DNA of 19 patients from 12 Spanish families with McArdle's disease (myophosphorylase deficiency). In 15 patients, the enzyme defect was documented histochemically in muscle, and in four the diagnosis was based on clinical and laboratory data. Three patients were homozygous and six were heterozygous for the nonsense mutation at codon 49 (R49X). Our findings indicate that the R49X mutation, which is common in English and American patients, is also present in Spanish patients with McArdle's disease, but at a lower frequency.

Adult↗