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Biomedical subjects

J Kagan

Publications and source records attributed to J Kagan.

At least 19 recordsLinked to original sources
PubMed1995

Homozygous deletions at 8p22 and 8p21 in prostate cancer implicate these regions as the sites for candidate tumor suppressor genes.

Frequent loss of an allele at specific chromosomal regions implicates these regions as sites of tumor suppressor genes (TSG) that become inactivated during tumor progression. We have studied chromosome 8p allele losses in 32 primary human prostate carcinomas with 16 polymorphic microsatellite sequences. Overall, 22 of 32 (69%) informative specimens showed loss of allele in at least one locus. The most frequent losses of heterozygosity (LOH) occurred at the LPL locus (46%) on chromosome 8p22 and at the D8S360 (45%) and NEFL (43%) loci on chromosome 8p21. Homozygous deletions were detected at the LPL and NEFL loci at 8p22 and 8p21, respectively. The minimal region with frequent LOH and homozygous deletion, around the LPL locus, was restricted between the MSR locus and the D8S258 marker, separated by less than 9 cM. The second region was restricted between markers D8S1128 and D8S131 separated by 12 cM. The results suggest the existence of two chromosome 8p sites for candidate TSGs in prostate cancer.

Alleles↗
PubMed1995

Standardization of absolute CD4+ lymphocyte counts across laboratories: an evaluation of the Ortho CytoronAbsolute flow cytometry system on normal donors.

The Ortho CytoronAbsolute is a flow cytometer designed to provide direct absolute counts of lymphocytes and their subsets from a single instrument. This study was designed to determine the performance of four geographically separated CytoronAbsolute instruments using 24-h-old, shipped, whole blood samples and to compare the results obtained on the CytoronAbsolute to those obtained using combinations of hematology instruments and other flow cytometers. The absolute count feature of the CytoronAbsolutes located at the four sites were cross calibrated and gave across-site coefficients of variation (CVs) of <4.0% for absolute count and 8.2% for absolute lymphocyte count. The calibration was stable for at least 2 months. Absolute lymphocyte counts and lymphocyte percentage immunophenotypes were determined on blood from 50 healthy human immunodeficiency virus (HIV)-seronegative donors. There were no significant site-to-site differences (each P > .05) in CD3+/CD4+ absolute lymphocyte counts determined on the CytoronAbsolute. In contrast, there was a significant site-to-site difference (P < .001) between sites 2 and 3 and sites 3 and 4 in the absolute CD3+/CD4+ lymphocyte counts determined via the conventional method of combining a flow cytometry-derived percentage with a hematology instrument-derived lymphocyte count. There was no significant difference (P = .388) in CD3+/CD4+ lymphocyte percent determinations between the CytoronAbsolute and the FACScan or Profile II flow cytometers used in this study. These results demonstrate that different operators can cross calibrate CytoronAbsolutes for absolute CD3+/CD4+ lymphocyte subset determinations, even over large geographic distances.

CD4 Lymphocyte Count↗
PubMed1995

Cardiac function and behavioral reactivity during infancy.

Longitudinal cardiac data from the end of the fetal period to 21 months of age were examined for change and stability over age and relations to the temperamental characteristics of high and low reactivity at 4 months of age and fear to the unfamiliar in the second year. Heart period and power in the cardiac spectra changed dramatically over the first 2 years, and individual differences were not preserved until 9-14 months of age. Sleep heart period at 2 weeks of age and low frequency power at 2 months of age were better predictors of the temperamental categories than later measures of the same variables, suggesting that cardiac function early in life may be an especially sensitive index of temperamental qualities.

Adult↗
PubMed1995

Interlaboratory variability of CD8 subset measurements by flow cytometry and its applications to multicenter clinical trials. NAID/NICHD Women and Infants Transmission Study Group.

Recent studies have demonstrated the utility of measuring subsets of CD8+ T cells as prognostic markers in epidemiology cohort studies of human immunodeficiency virus (HIV)-infected patients. Most of these studies evaluating the value of CD8+ T-cell subsets have been performed at single centers, and few data are available on variability in the measurement of the CD8+ cell populations in multicenter trials. In the current study, we addressed this question by evaluating interlaboratory variability from the five laboratories enrolled in the Women and Infants Transmission Study sponsored by the National Institutes of Health. This study evaluated 35 HIV-positive and 28 HIV-negative proficiency testing samples sent to the laboratories for evaluation. The study focused on the robust coefficient of variation (RCV) for CD38 (11%), HLA-DR (21%), and CD57 (15%) expression on the CD8+ population. Data from the current study indicated that the variability in these measurements is greater than that for CD3+ CD4+ (RCV, 5%) and CD3+ CD8+ (RCV, 5%) cells. Knowledge of the variability of the CD8+ subset measurements should guide investigators in the design and analysis of clinical trials and epidemiology studies. Ability to obtain improved interlaboratory agreement on CD8+ subset measurements will facilitate further evaluation of these markers in HIV studies.

CD3 Complex↗
PubMed1995

Temperament and craniofacial variation in the first two years.

High levels of circulating glucocorticoids in fetal animals are associated with inhibited development of the lateral processes of the maxilla, or upper jaw, as these bones grow toward midline union early in gestation. This inhibition can prevent fusion and lead to the formation of cleft palate. Mouse strains are differentially susceptible to this effect. These strains also differ in behavioral and physiological characteristics that are analogous to those we have observed in 2 temperamental groups of children, analogies that prompted the current study. Infant temperament was assessed using behavioral observation at 4 months, and the ratio of upper facial width (bizygomatic breadth across the cheekbones) to height of the head and face was measured at 14 and 21 months. High reactive 4-month-old infants, who are predisposed to becoming timid, inhibited toddlers, had smaller bizygomatic ratios (narrower faces) at both 14 and 21 months compared to their low reactive peers, who are predisposed to becoming outgoing, uninhibited children. Differences in facial width were modest though significant and not attributable to overall stature.

Arousal↗
PubMed1994

Loss of heterozygosity in human primary prostate carcinomas: a possible tumor suppressor gene at 7q31.1.

We studied loss of heterozygosity (LOH) on human chromosome 7q to determine the location of a putative tumor suppressor gene (TSG) in human primary prostate carcinomas. Samples were obtained from 16 primary prostate carcinomas surgically removed from patients at The University of Texas M. D. Anderson Cancer Center. Paired normal and tumor DNAs were used as template for PCR amplification of a set of 14 CA microsatellite repeats on 7q21-qter. Twelve of 16 cases studied had LOH at one or more loci on 7q. Eighty-three percent LOH (five of six informative cases) was detected with D7S522 at 7q31.1-7q31.2. Percentage of LOH was normally distributed around D7S522. The high incidence of LOH in primary prostate carcinomas suggests that there is a TSG relevant to the development of prostate cancers at 7q31.1-31.2, confirming our previous functional evidence for a TSG at this location. Further research needs to be conducted to establish the identity and function of this putative TSG.

Carcinoma↗
PubMed1994

Joining of recombination signals on the der 14q- chromosome in T-cell acute leukemia with t(10;14) chromosome translocation.

Sequence analysis of the translocation breakpoint junctions on the der(14q-) chromosome in six patients carrying a t(10;14) chromosome translocation revealed that the breakpoint occurred 5' to the HOX11 protooncogene at the breakpoint cluster region. HOX11 coding sequence was not effected. The translocation resulted in the joining of the V-(D)-J recombination signals 5' to the T-cell receptor D delta 2 segment on chromosome 14 with chromosome 10 at a location within a heptamer-like sequence. At the breakpoint junctions, the insertion of extra nucleotides, N-nucleotides, including P-nucleotides, was evident. The mechanism involved in this process is discussed.

Base Sequence↗
PubMed1994

Photosensitized cross-linking and cleavage of pBR322 and M13 DNA: comparison of 4,4',6-trimethylangelicin and 3-carbethoxypsoralen.

The furocourmarins 3-carbethoxypsoralen (3-CP) and 4,4',6-trimethylangelicin (TMA) were generally believed to be incapable of cross-linking DNA upon irradiation with ultraviolet light. Denaturation of photosensitized pBR322 DNA, either supercoiled or previously linearized with a restriction enzyme, proved that 3-CP was indeed monofunctional, but that TMA produced cross-links. Identical conclusions were reached with double stranded M13 DNA which had been linearized with EcoR 1. Both sensitizers also induced partial DNA cleavage. In contrast to 3-CP, photosensitization with TMA made the DNA resistant to enzymatic cleavage.

Bacteriophage M13↗
PubMed1994

Crosslinking and cleavage of pBR322 DNA photosensitized by 7-methylpyrido[3,4-c]psoralen.

7-Methylpyrido[3,4-c]psoralen (7-MPP) had been designed to be a monofunctional sensitizer in which the pyrone double bond, being engaged in a pyridine ring, would be incapable of participating in the formation of a cyclobutane ring with a DNA component. However, one example of photosensitization of thymine-thymine dimer formation in DNA by 7-MPP had been reported. This paper proves that 7-MPP can sensitize interstrand crosslinks in pBR322 DNA. It also proves that 7-MPP photosensitizes double strand cleavage reactions in the DNA with an unusually large degree of site selectivity.

Carcinogens↗
PubMed1994

On the nature of emotion.

This essay has tried to make three points. First, humans are capable of a large number of affect states (the exact number is not yet known), each marked by a distinct profile of physiology, cognition, and behavior, and each requiring a distinct name. Second, a distinction should be made among acute emotions, chronic moods, and temperamental vulnerabilities to a particular emotion state. Finally, research on human affects will profit from a return to, and a reinterpretation of, Freud's suggestion of unconscious affect states. Such inquiry would provide a corrective to the current reliance on the verbal reports of phenomenal states on questionnaires or in interviews as either the only, or the primary, index of an emotion. Continued use of this strategy will limit analyses to a small number of heterogeneous states that happen to have a popular English name and will retard discovery of the larger number of affect states that are of significance for human function. Discovery of these states will require use of new sources of evidence to supplement popular ones, including facial and postural expressions, muscle tension, EEG, vagal tone, heart-rate changes, blood pressure, GSR, facial temperature, and blood or saliva indexes of norepinephrine, opioids, and cortisol. When the cosmologist James Peebles was asked to guess the exact numerical answers to a series of astronomical puzzles, like the age of the universe or of a distant star, he replied, "If someone gave me on a tablet of clay the answer and the numbers, I would be disappointed. I would throw it away because the great discoveries are not going to be a final number, but the method you come to apply to learn that number."

Adaptation, Psychological↗
PubMed1993

Assessment of the effects of instrumentation, monoclonal antibody, and fluorochrome on flow cytometric immunophenotyping: a report based on 2 years of the NIAID DAIDS flow cytometry quality assessment program.

This study of the effect on CD4%, CD8%, CD3+8+%, and CD3% of flow cytometer, monoclonal antibody, and fluorochrome was based on 71 whole-blood samples, each evaluated by 42 to 59 laboratories during 2 years of a flow cytometry quality assessment program. For the 24 HIV-positive specimens, FACScans produced significantly lower CD4% values than EPICS-Cs or EPICS Profiles, and for the 47 HIV-negative specimens, FITC was associated with significantly lower CD4% values than PE or RD1, but differences were never larger than 2% and regressions accounted for only 3-12% of the variability. The labs using the most common CD4 technique had significantly higher between-laboratory variability than all other labs grouped together. For both CD8 and CD3+8+, measurements on FACScans were significantly higher than measurements on EPICS, and measurements using Leu2 were significantly higher than measurements using T8, with regressions accounting for 12-31% of the variability. The machine differences in medians were 3-7% for labs using Leu2-FITC. It might be worthwhile to discourage the use of Leu2-FITC for measuring CD8% but no change in instrument, monoclonal antibody, or fluorochrome would greatly improve interlaboratory agreement on CD4%.

Antibodies, Monoclonal↗
PubMed1993

Photosensitized cleavage and cross-linking of pBR322 DNA with khellin and visnagin.

The naturally occurring furanochromones khellin and visnagin have received considerable attention, largely because of their vasodilatory properties and of their ability (particularly that of khellin) to induce skin pigmentation upon ultraviolet light treatment of patients suffering from vitiligo. There are conflicting statements in the literature on whether or not they are capable of cross-linking DNA photochemically. Supercoiled and linear pBR322 DNA was used to probe this reaction. The results showed that both khellin and, to a greater extent, visnagin photosensitized DNA cross-linking. In addition, both photosensitizers induced extensive DNA cleavage.

Cross-Linking Reagents↗
PubMed1993

DNA cleavage, antiviral and cytotoxic reactions photosensitized by simple enediyne compounds.

Very potent antibiotic antitumor natural products contain a enediyne moiety which, upon thermal activation, is capable of abstracting hydrogens from DNA. 1,6-Diphenyl-3-hexene-1,5-diyne was selected as a candidate for inducing DNA strand breaks photochemically. Easily interconverted with light, both geometric isomers 1 and 2 were expected to be phototoxic. As anticipated, they photosensitized the production of strand breaks in double-stranded supercoiled pBR322, and in single-stranded M13 DNA. The DNA cleavage reactions were favored by the presence of oxygen and were inhibited by ethanol. Preliminary experiments with the (Z)-isomer indicated moderate light-dependent antiviral activity against human immunodeficiency virus (HIV), Sindbis virus, and mouse cytomegalovirus. The enediynes were cytotoxic to Escherichia coli, a gram-negative organism, to Streptococcus faecalis, a gram-positive organism, to Daphnia magna and to fish (Pimephales promelas), but only in the presence of light. The production of o-terphenyl, the expected product of Bergman cyclization of 1, could not be confirmed. However, both 1 and 2 photosensitized the formation of singlet oxygen and of superoxide anion radical, and photodynamic reactions could have been responsible for some of the phototoxic reactions observed.

3T3 Cells↗
PubMed1993

A 3-year follow-up of children with and without behavioral inhibition.

OBJECTIVE: Previous work suggested that children of parents with panic disorder and agoraphobia were likely to be classified as behaviorally inhibited and that behaviorally inhibited children were likely to develop anxiety disorders. Although these findings suggested that "behavioral inhibition to the unfamiliar" may be associated with risk for anxiety disorders in children, longitudinal data were needed to confirm the initial impressions. METHOD: Using DSM-III structured interviews, the authors examined psychiatric disorders at 3-year follow-up in children of two independently ascertained, previously described, and preexisting samples of children. One sample was cross sectional and clinically derived (Massachusetts General Hospital at-risk sample), and the other was epidemiologically derived and longitudinal (Kagan et al. Longitudinal Cohort). RESULTS: Analyses of follow-up findings revealed significant differences between inhibited and not inhibited children in the rates of multiple > or = 4 psychiatric disorders, multiple > or = 2 anxiety disorders, avoidant disorder, separation anxiety disorder, and agoraphobia. Among inhibited children, the rates of anxiety disorders increased markedly from baseline to follow-up assessments, attaining statistical significance for multiple > or = 2 anxiety disorders and avoidant disorder. Our findings also show there were significant differences between inhibited and not inhibited children in the emergence of multiple > or = 2 anxiety disorders, avoidant disorder, and separation anxiety disorder in children who did not have these diagnoses at baseline. CONCLUSIONS: These findings indicate that inhibited children are at high risk for developing childhood-onset anxiety disorders and provide additional support for the hypothesis that behavioral inhibition is a predictor of later anxiety disorder.

Adolescent↗
PubMed1993

Phototoxicity of (1H-indenyl)thiophenes.

The (1H-indenyl)thiophene derivatives 2 and 3 were recently reported to be excellent singlet oxygen sensitizers, comparable to alpha-terthienyl (1). The phototoxicity of these compounds was compared, using human erythrocytes, Aedes aegypti mosquito larvae, Daphnia magna, and fish (fathead minnows, Pimephales promelas). The known ranking of the photooxidation properties was found to be a good predictor of phototoxic properties in erythrocytes and mosquito larvae but not in daphnias. All three compounds photosensitized the cleavage of supercoiled pBR322 DNA to the same extent.

Aedes↗