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Biomedical subjects

J Kagan

Publications and source records attributed to J Kagan.

At least 109 records · Page 6Linked to original sources
PubMed1990

Functional human T cell-B cell hybridomas established from fusion of normal T cells and an EBV-transformed B cell line.

Human T cell-B cell hybridomas containing 92 chromosomes were derived by fusing normal stimulated CD-depleted T cells with the EBV-transformed human B cell line 729-HF. These hybridomas coexpressed the T cell surface markers CD3, CD8, and CD2 and the B cell surface antigens CD19, CD20, CD23, DR, and DQ. They weakly and variably expressed surface IgM and TCR. Genomic analysis revealed the presence of rearranged Ig genes as well as beta-T cell receptor genes that could be ascribed to the B and T cell parent, respectively. Analysis of TCR rearrangement suggests that the T-B hybridomas are, in fact, subclones of a single dominant clone. Although the hybrids expressed CD8 and not CD4, following preincubation with PWM, some the of clones induced IgG synthesis from normal B cells while the parent B cell line failed to demonstrate this activity. Stimulation of the hybridomas with PMA down-regulated the T cell lineage-specific antigen display (CD3, CD8, and TCR) and increased IgM production from the hybrids without changing B cell surface antigen display. These hybridomas may be useful to dissect the steps involved in the ultimate commitment of a cell to the B or T cell lineages and will be made available to interested investigators.

Antigens, CD↗
PubMed1990

Light-dependent cytotoxic reactions of anthracene.

Anthracene is a photodynamic compound in vitro. In the presence of oxygen, it is known to generate singlet oxygen and participate in Type II reactions. In aqueous solution, it also participates in Type I reactions, such as in the photoreduction of cytochrome c, which can be suppressed by superoxide dismutase. In argon, direct photoreduction of cytochrome c also takes place. Anthracene induces the photodynamic hemolysis of human erythrocytes and inactivates Escherichia coli cells photodynamically. By using a series of E. coli strains differing in DNA repair capabilities and catalase proficiency, sensitivity to inactivation by anthracene plus NUV was correlated with catalase deficiency rather than with particular repair deficiencies. The fact that carotenoid genes cloned and expressed in E. coli offered partial protection suggests that the membrane may be one possible target for inactivation by anthracene plus NUV. Anthracene plus NUV inactivated Haemophilus influenzae transforming DNA and led to nicking of supercoiled pBR322 DNA in vitro. In vivo, therefore, anthracene is a phototoxic molecule whose cytotoxicity could be the result of damage to more than one target.

Anthracenes↗
PubMed1990

The hemolysis of erythrocytes by singlet oxygen generated in the gas phase.

Many sensitizers cause photodynamic hemolysis of erythrocytes. As these sensitizers usually participate in Type I as well as Type II processes, the determination of the mechanism(s) of photosensitized hemolysis is always ambiguous. Here, human erythrocytes were proved to hemolyze upon treatment with singlet oxygen (1 delta g) generated with fluoranthene in the gas phase. These conditions rigorously exclude the participation of superoxide anion. The standard diagnostic tests for singlet oxygen (enhanced effect in D2O and protection by NaN3) gave the anticipated results when the erythrocytes were treated with 1O2 generated in the gas phase. When the erythrocytes were irradiated in a buffer solution containing fluoranthene, the results of the diagnostic tests depended on the sensitizer concentration.

Hemolysis↗
PubMed1989

Physical and physiological correlates of behavioral inhibition.

Previous investigations have suggested that the temperamental quality of inhibition is related to the threshold of reactivity to unfamiliar events within certain limbic structures. In earlier work, children in three independent samples who had been selected to be inhibited were more likely to have blue than brown eyes, whereas uninhibited children were more likely to have brown eyes. The present study, which selected two-year-old children on the basis of eye color (blue or brown) rather than behavior, found a significant association between blue eyes and behavioral inhibition, and between brown eyes and an uninhibited style. Although the inhibited children were more likely to have a high and stable heart rate than were the uninhibited children, there was no relation between eye color and these cardiac measures. Several interpretations of the association between these temperamental categories and iris pigmentation are proposed.

Arousal↗
PubMed1989

Direction of gaze and emergence of speech in the second year.

Orienting to the right member of a pair of identical pictures increased monotonically with age in a longitudinal sample of 14 infants seen monthly from 13 to 22 months. The magnitude of the correlation between this orientation bias and a measure of language development also rose with age reaching a peak at 20 months and then declining. It was suggested that the acceleration of vocabulary and maturational changes in the central nervous system that occur between 16 and 22 months are associated with a special excitatory state in the temporal cortex of the left hemisphere.

Dominance, Cerebral↗
PubMed1989

The light-dependent cytotoxicity of benzo[a]pyrene: effect on human erythrocytes, Escherichia coli cells, and Haemophilus influenzae transforming DNA.

In vitro, the photodynamic compound benzo[a]pyrene (BAP) generates singlet oxygen efficiently when irradiated in organic solvents. It also photogenerates superoxide anion radical in water and can act as a photoreducing agent in the absence of oxygen. In vivo, the hemolysis of human erythrocytes, the inactivation of Escherichia coli cells representing a series of strains differing in excision repair and catalase proficiency, and the inactivation of Haemophilus influenzae transforming DNA activity were used to characterize the phototoxicity of BAP in the presence of near-UV light (290-400 nm). The results are consistent with BAP behaving as a photosensitizer that generates both superoxide and singlet oxygen, and that damages chiefly membranes. DNA does not seem to be a major target in the phototoxic reactions investigated.

Benzo(a)pyrene↗
PubMed1989

Photosensitization with alpha-terthienyl: the formation of superoxide ion in aqueous media.

It is well known that alpha-terthienyl generates singlet oxygen in organic solvents with high quantum yields. In an aqueous medium, the production of superoxide radical-anion is readily detected by comparing the reduction of ferricytochrome c or nitro blue tetrazolium in the presence and in the absence of superoxide dismutase. Electron transfer reactions from the electronically excited sensitizer are also detected in an argon atmosphere.

Cytochrome c Group↗
PubMed1989

Clustering of breakpoints on chromosome 10 in acute T-cell leukemias with the t(10;14) chromosome translocation.

The T-cell receptor (TCR) alpha/delta chain locus on chromosome 14q11 is nonrandomly involved in translocations and inversions in human T-cell neoplasms. We have analyzed three acute T-lymphoblastic leukemia samples carrying a t(10;14)(q24;q11) chromosome translocation by means of somatic cell hybrids and molecular cloning. In all cases studied the translocation splits the TCR delta chain locus. Somatic cell hybrids containing the human 10q+ chromosome resulting from the translocation retain the human terminal deoxynucleotidyltransferase gene mapped at 10q23-q24 and the diversity and joining, D delta 2-J delta 1, regions of the TCR delta chain, but not the V alpha region (variable region of the TCR alpha chain), demonstrating that the split occurred within the V alpha-D delta 2 region. Molecular cloning of the breakpoint junctions revealed that the TCR delta chain sequences involved are made from the D delta 2 segment. The chromosome breakpoints are clustered within a region of approximately 263 base pairs of chromosome 10. The results suggest that the translocation of the TCR delta chain locus to a locus on 10q, which we have designated TCL3, results in deregulation of this putative oncogene, leading to acute T-cell leukemia.

Base Sequence↗
PubMed1989

Involvement of the TCL5 gene on human chromosome 1 in T-cell leukemia and melanoma.

We analyzed a t(1;14)(p32;q11) chromosomal translocation in a human lymphohemopoietic stem cell line derived from a patient with acute T-lymphoblastic leukemia. The chromosomal joining on the 1p+ chromosome occurred at the T-cell receptor delta diversity (D delta 2) segment, and the reciprocal chromosomal joining on the 14q- chromosome occurred at the T-cell delta diversity segment D delta 1. The involvement of delta diversity segments at the translocation junctions suggests that the translocation occurred during an attempt at D delta 1-D delta 2 joining in a stem cell. The segment of chromosome 1 at band p32, adjacent to the chromosomal breakpoint, encodes a transcriptional unit designated TCL5 (T-cell leukemia/lymphoma 5). The differential expression of the TCL5 RNA transcripts in this lymphohemopoietic stem cell line relative to several other T- and B-cell lines suggests that TCL5 gene expression is an integral event in the pathogenesis of the T-cell leukemia. Rearrangement of the TCL5 locus in a human melanoma cell line carrying a del(1p32) further implies that the TCL5 gene may play a role in malignant transformation.

Base Sequence↗
PubMed1989

The chromosome 11 region flanking the t(11;14) breakpoint in human T-ALL is deleted in Wilms' tumor hybrids.

Human chromosomal band 11p13 has been implicated in T cell malignancies carrying t(11;14)(p13;q11) reciprocal translocations and has also been associated with Wilms' tumor and aniridia in a mechanism characterized by overlapping hemizygous constitutional deletions spanning this region. Using probes derived from the T cell receptor delta gene, we have cloned the chromosomal breakpoint in an acute T cell leukemia (T-ALL). Southern blotting analyses of mouse-human somatic cell hybrids from this human T-ALL sample and Chinese hamster-human somatic cell hybrids derived from Wilms' tumor lines have indicated that the 11p13 locus, tcl-2, juxtaposed to the TCR (T cell receptor) delta locus in T cell leukemia, is within the constitutional deletion of two Wilms' tumor-aniridia cases.

Animals↗
PubMed1989

Inhibited and uninhibited types of children.

An initial group of 100 children who were not selected a priori on any behavioral features were observed in laboratory settings at 14, 20, 32, and 48 months and their behaviors coded for inhibition and lack of inhibition to the unfamiliar. The children who had been extremely inhibited or uninhibited at both 14 and 20 months differed significantly at 4 years of age in behavior and cardiac acceleration to cognitive stress. However, for the entire sample, there was no significant relation between degree of inhibited behavior at 14 or 20 months, on the one hand, and inhibition at 4 years of age, on the other, nor any relation between behavior and heart rate acceleration. These results suggest that the constructs inhibited and uninhibited to the unfamiliar refer to children who fall at the extremes of a phenotypic continuum from shyness and restraint to sociability and affective spontaneity.

Cognition↗
PubMed1988

Biological bases of childhood shyness.

The initial behavioral reaction to unfamiliar events is a distinctive source of intraspecific variation in humans and other animals. Two longitudinal studies of 2-year-old children who were extreme in the display of either behavioral restraint or spontaneity in unfamiliar contexts revealed that by 7 years of age a majority of the restrained group were quiet and socially avoidant with unfamiliar children and adults whereas a majority of the more spontaneous children were talkative and interactive. The group differences in peripheral physiological reactions suggest that inherited variation in the threshold of arousal in selected limbic sites may contribute to shyness in childhood and even extreme degrees of social avoidance in adults.

Age Factors↗
PubMed1988

Behavioral inhibition in children of parents with panic disorder and agoraphobia. A controlled study.

To investigate the role of "behavioral inhibition to the unfamiliar" as an early temperamental characteristic of children at risk for adult panic disorder and agoraphobia (PDAG), we compared children of parents with PDAG with those from psychiatric comparison groups. Fifty-six children aged 2 to 7 years, matched for age, socioeconomic status, ethnic background, and ordinal position, were blindly evaluated at the Harvard Infant Study laboratory, Cambridge, Mass. The rates of behavioral inhibition in children of probands with PDAG, with or without comorbid major depressive disorder (MDD), were significantly higher than for our comparison group without PDAG. Further, the data suggest a progression of increasing rates of inhibition from the comparison group without MDD (15.4%), to MDD (50.0%), and to comorbid PDAG and MDD (70%) and PDAG (84.6%). In contrast, the rate of behavioral inhibition in children of probands with MDD did not meaningfully differ from the comparison group without MDD. Behavioral inhibition to the unfamiliar, as defined and measured in the previous work of the Harvard Infant Study program, is highly prevalent in the offspring of adults in treatment for PDAG. These children appear to be at risk for distress and disability in childhood and also perhaps for development of psychiatric disorder in later childhood and aulthood.

Adolescent↗
PubMed1988

Childhood derivatives of inhibition and lack of inhibition to the unfamiliar.

Behavioral and physiological assessments of 41 7 1/2-year-old children who had been selected to be inhibited or uninhibited at 21 months and observed again at 4 and 5 1/2 years revealed that each of the 2 original behavioral profiles predicted theoretically reasonable derivatives. A majority of the formerly shy, timid children became quiet and socially avoidant in unfamiliar social situations, while a majority of the formerly sociable children became talkative and interactive with peers and adults. Absolute heart-rate and cortisol level at 7 1/2 years were not as discriminating of the 2 behavioral groups as they had been 2 years earlier.

Arousal↗
PubMed1988

Role of cloned carotenoid genes expressed in Escherichia coli in protecting against inactivation by near-UV light and specific phototoxic molecules.

Genes controlling carotenoid synthesis were cloned from Erwinia herbicola and expressed in an Escherichia coli strain. Carotenoids protect against high fluences of near-UV (NUV; 320 to 400 nm) but not against far-UV (200-300 nm). Protection of E. coli cells was not observed following treatment with either psoralen or 8-methoxypsoralen plus NUV. However, significant protection of cells producing carotenoids was observed with three photosensitizing molecules activated by NUV (alpha-terthienyl, harmine, and phenylheptatriyne) which are thought to have the membrane as an important lethal target. Protection of carotenoid-producing cells against inactivation was not observed with acridine orange plus visible light but was seen with toluidine blue O plus visible light.

Acridine Orange↗