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Biomedical subjects

J Curry

Publications and source records attributed to J Curry.

At least 37 records · Page 2Linked to original sources
PubMed1996

Mutational specificity and cancer chemoprevention.

Mutational specificity describes the composite of all of the genetic alterations in a collection of mutations arising from a specific treatment. The information includes not only the nature of the genetic change (e.g., a base substitution or a frameshift), but also information about nucleotide position and hence the DNA context. As both the type of DNA damage and its position can be expected to reflect the nature of the chemical and physical mutagen, mutational specificity can be expected to provide insights into mechanisms of mutation. Conversely, mutational spectra should also provide insights into the identity of the mutagen. Indeed, the pioneering work on mutational specificity in Escherichia coli indicates that each physical or chemical treatment produces a unique spectrum of mutations. With the application of biotechnology to the field of genotoxicology, the database of sequenced mutations has become quite substantial. Both in vitro and in vivo data has been obtained following exposure to a variety of agents. In this communication we will critically assess whether the reality of mutational specificity has fulfilled the expectations and to examine what potential remains to be explored, especially in the area of monitoring human populations. The usefulness of both mutational spectra analysis and population monitoring with regards to chemoprevention are discussed.

Animals↗
PubMed1995

Cerebellar granule neurons develop elevated calcium responses when treated with interleukin-6 in culture.

In humans, elevated levels of cytokines are associated with several diseases (including HIV infection and Down Syndrome) that result in developmental abnormalities. Overexpression of interleukin-6 (IL-6) in the central nervous system has been shown to cause extensive neuronal abnormality in mice that becomes more evident with maturation. However, it is difficult to separate direct effects of IL-6 on the developing neurons of an intact animal from indirect effects involving effects on other cell types that possess cytokine receptors, such as microglia and astrocytes. We have found that IL-6 treatment of rat cerebellar granule neurons developing in the absence of other cell types in culture results in the persistence of large, depolarization or neurotransmitter-induced calcium transients, that are normally observed only in immature neurons. The cause of this appears to be the persistence of a calcium-induced calcium release (CICR) component of the calcium response to stimulation. This basic abnormality in neuronal development may contribute to the developmental abnormalities associated with human syndromes that involve elevated cytokine levels.

Age Factors↗
PubMed1995

Determination of hprt mutant and mutation frequencies and the molecular characterization of human derived in vivo T-lymphocyte mutants.

Using a T-lymphocyte clonal assay, 73 6-thioguanine resistant T-lymphocytes were isolated from two blood samples obtained 4 months apart from a 50-year-old male subject. Sixty-six of these mutants were characterized at the DNA sequence level using cDNA. One particular single base substitution was recovered a total of 23 times. The majority of T-cell receptors (TCR) of these mutants all share a common gamma-TCR rearrangement, and thus likely represent a single mutational event that underwent clonal expansion in vivo. Siblings of this clone were recovered in both collections. Three other single base substitutions were also recovered more than once. In two of the three cases, the mutants were also found to be clonally related, while in one case they were not. A number of identical exon loss events were also recovered, yet none of these were clonally related. This probably reflects the multiple pathways by which these mutations can arise. The TCR data was used to correct the observed mutant frequency to produce an estimate of the actual mutation frequency. The two mutant frequencies, 18 x 10(-6) and 19 x 10(-6), obtained from the first and second sampling periods, respectively, can thus be corrected to yield true mutation frequency's of 12 x 10(-6) each.

Base Composition↗
PubMed1995

Analysis of point mutations in the hprt gene of cancer patients treated with radioimmunoglobulin therapy.

The mutagenic impact of various environmental and therapeutic agents can now be directly assayed in humans by the T-lymphocyte cloning assay. We have previously reported that following radioimmunoglobulin therapy, cancer patients exhibited increased mutant frequency of the hprt locus and an increased yield of large intergenic deletions compared to unexposed controls. Here we report the results of the analysis of 26 independent hprt mutations in nine cancer patients who underwent radioimmunoglobulin therapy. The majority of mutations (52%) had lost exon sequences from the mRNA. The remaining mutations were 20% small deletions and frameshifts and 28% base substitutions. The type of mutations observed were similar to those seen in unexposed controls. The site distribution of the mutations, however, indicates that some sequence contexts may be more sensitive to radiation mutagenesis than others.

Adult↗
PubMed1995

Older age and the underreporting of depressive symptoms.

OBJECTIVE: To determine whether older age is associated with a decrease in self-reported depressive symptoms, independent of examiner-rated symptoms, in inpatients with major depression. DESIGN: Survey study. SETTING: Inpatient psychiatric units at a university medical center. PATIENTS: Eligible subjects were those over 20 years of age with a primary diagnosis of DSM-III-R major depression. Participation was sought from all subjects over 60 years of age and from every second or every third younger subject, depending on rater availability. Of 137 eligible subjects, 97 completed all study measures. MEASUREMENTS: The Beck Depression Inventory (BDI), as a measure of self-reported depressive symptoms, was the dependent variable. The Hamilton Rating Scale for Depression (Ham-D) was used to assess examiner-rated symptoms. MAIN RESULTS: Older age (P = .03) was associated negatively and examiner-rated depressive symptoms (P = .0001) were associated positively with BDI score. Other variables, including gender, education, age of depression onset, and medical illness burden, were not independently associated with BDI. Examination of depressive symptom subtotals (psychologic/affective vs. somatic/neurovegetative) revealed that only the self-reported psychologic/affective subtotal was significantly associated with age (P = .0018). CONCLUSIONS: Some older patients with clinically significant depression underreport their symptoms. When asking older patients about depressive symptoms, clinicians should view negative responses only within larger clinical contexts and should obtain information from other sources as needed. Similar concerns must temper interpretation of research that relies on subject self-report to study depression in late life.

Age Factors↗
PubMed1995

The role and scope of data management in a changing health services delivery environment.

Data and information are essential to rational decision making and the good management of the health services delivery systems in any country. The restructuring of health systems world-wide is impacted by these concepts. The information systems necessary to provide data and information can be characterized by a number of interdependent domains. Data Management is central because data provides the binding principle: Applications are processing Data, Technology is transferring data, Methodology is identifying how data is captured and where it is used in order to minimize the cost of data as a resource. The whole purpose is to serve the Business of Health Services Delivery. Each domain is interdependent with the others at an intersection between the domains.

Database Management Systems↗
PubMed1994

International Commission for Protection Against Environmental Mutagens and Carcinogens. Working paper no. 2. Spontaneous mutations in mammalian cells.

Spontaneous or background mutation in mammals plays an important role in both medical and evolutionary contexts. However, establishing mutation frequencies or rates has not always been easy. When the field of mammalian mutagenesis was in its infancy, the word "variant" rather than "mutant" was often used because the genetic nature of the observed phenotypic alterations could not be adequately proven. Nowadays numerous target genes have been identified in which mutant frequencies can be measured, and occasionally even rates can be estimated. Indeed, the genetic basis for 'variants' now often comes from direct DNA sequencing. This review describes the most often used and best understood genetic markers for mutation research and examines their usefulness. In addition, mutational specificity is compared for several loci and the use of DNA-sequence data in determining the origins of spontaneous mutation is also discussed. An important observation is that spontaneous mutation frequencies of similarly sized genes can vary by more than an order of magnitude. Chromosomal location, the nature of the gene product and mutational specificity may offer a partial explanation.

Animals↗
PubMed1994

Asymmetry and skin pigmentary anomalies in chromosome mosaicism.

We report six persons mosaic for a chromosome anomaly. All were mentally retarded and dysmorphic. Unilateral or asymmetrical features were found in all cases, in one an unusual transverse terminal limb anomaly, and in the others various degrees of hemiatrophy of the left side of the body. Five of the subjects had skin pigmentary anomalies which were distributed in the lines of Blaschko. The abnormal cell lines found were ring chromosome 22, trisomy 22, a large acrocentric marker, a deletion of 18q, a deletion of 8q, and triploidy. In four cases the clinical diagnosis was only confirmed by skin biopsy. In one case low level mosaicism in blood was fortuitously detected because of cytogenetic fragile X screening and confirmed in a skin biopsy. The sixth case was of dynamic mosaicism of a non-mosaic deletion 18q with a chromosome 18 derived marker present in a proportion of cells. Chromosome mosaicisn may cause subtle and asymmetrical clinical features and can require repeated cytogenetic investigations. The diagnosis should be actively sought as it enables accurate genetic counselling to be given.

Abnormalities, Multiple↗
PubMed1993

Unusual sequence of group 3 LEA (II) mRNA inducible by dehydration stress in wheat.

A cDNA clone, pMA1949, detects two mRNA species in wheat seedling tissue that are late embryogenesis-abundant (LEA) and dehydration stress-inducible. Sequence analysis of the pMA1949 clone shows it to be a 991 bp partial cDNA encoding a polypeptide of 317 amino acids with homology to two group 3 LEA proteins, carrot (DC8) and a soybean protein encoded by pGmPM2 cDNA. Molecular analysis of the deduced protein reveals a 33 kDa acidic and extremely hydrophilic protein with potential amphiphilic alpha-helical regions. In addition, the protein contains eleven similar, contiguous repeats of 11 amino acids, which are separated by 118 amino acids from two additional and unique repeats of 36 residues each at the carboxyl end of the protein. Comparisons of sequences of reported group 3 LEA proteins revealed that there are two types, separable by sequence similarity of the 11 amino acid repeating motifs and by the presence or absence of a certain amino acid stretch at the carboxyl terminus. Based on results from these comparisons, we propose a second type of group 3 LEA proteins, called group 3 LEA (II).

Amino Acid Sequence↗
PubMed1993

Coamplification of hprt cDNA and gamma T-cell receptor sequences from 6-thioguanine resistant human T-lymphocytes.

The nature of mutation at the HPRT locus in human T-lymphocytes in vivo is currently a subject of considerable interest. Determination of clonality in individual mutant T-lymphocytes is essential for the proper interpretation. This requires the molecular analysis of their respective T-cell receptors (TCR). We have developed a polymerase chain reaction (PCR)-based method for coamplification of hprt cDNA and the rearranged gamma T-cell receptor genes from crude cell lysates of individual 6-thioguanine resistant human T-lymphocytes. Following reverse transcription to produce hprt cDNA, the crude cell lysate is treated with proteinase K and subjected to a primary PCR with two sets of amplification primers, one specific for the hprt cDNA and the other for the rearranged gamma TCR gene. A secondary round of PCR, employing appropriate sets of nested amplification primers, are then used to produce sufficient quantities of DNA for both the sequencing and restriction fragment length analysis, of the hprt cDNA and gamma TCR gene respectively.

Adult↗