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J Petrini

Publications and source records attributed to J Petrini.

15 recordsLinked to original sources
PubMed2000

Radiosensitivity in Nijmegen Breakage Syndrome cells is attributable to a repair defect and not cell cycle checkpoint defects.

Cells derived from Nijmegen Breakage Syndrome (NBS) patients display radiosensitivity and cell cycle checkpoint defects. Here, we examine whether the radiosensitivity of NBS cells is the result of a repair defect or whether it can be attributed to impaired checkpoint arrest. We report a small increased fraction of unrejoined double strand breaks and, more significantly, increased chromosome breaks in noncycling NBS cells at 24 h after irradiation. One of the NBS lines examined (347BR) was atypical in showing a nearly normal checkpoint response. In contrast to the mild checkpoint defect, 347BR displays marked y-ray sensitivity similar to that shown by other NBS lines. Thus, the gamma-ray sensitivity correlates with the repair defect rather than impaired checkpoint control. Taken together, the results provide direct evidence for a repair defect in NBS cells and are inconsistent with the suggestion that the radiosensitivity is attributable only to impaired checkpoint arrest. 347BR also displays elevated spontaneous damage that cannot be attributed to impaired G2-M arrest, suggesting a function of Nbsl in decreasing or limiting the impact of spontaneously arising double strand breaks.

Abnormalities, Multiple↗
PubMed1992

Signaling function of reconstituted CD16: zeta: gamma receptor complex isoforms.

Natural killer cells express an Fc receptor for IgG (CD16) in association with disulfide-linked dimers composed of two homologous subunits: the zeta chain of the T cell antigen receptor complex and the gamma chain of the mast cell/basophil Fc receptor for IgE. The ability of zeta and gamma to transduce CD16-mediated activation signals was compared by reconstituting distinct CD16 receptor isoforms composed of various combinations of zeta- and gamma-containing dimers. Stably transformed non-hematopoietic and hematopoietic cell lines were established that expressed chimeric molecules comprising the extracellular domain of CD16 joined to the transmembrane and intracellular domains of zeta or gamma. Reconstituted CD16 receptor complexes triggered Ca2+ influx, tyrosine phosphorylation, and IL-2 production in stable transformants of the Jurkat T cell line. However, cross-linking of the CD16/gamma chimera induced a specific pattern of tyrosine phosphorylation and was more efficient at signal transduction than a CD16, zeta-zeta complex, suggesting that zeta and gamma cytoplasmic domains may be coupled to distinct tyrosine kinase pathways that differentially regulate CD16-mediated activation signals. By contrast, both CD16/zeta and CD16/gamma chimeric molecules were not functional in stable transformants of the fibroblast Chinese Hamster Ovary cell line, indicating a requirement for downstream signaling components present in hematopoietic cells. Finally, the zeta transmembrane domain appears to preferentially associate with CD16 rather than the CD3:TCR complex, suggesting that a hierarchy of molecular interactions governs NK and T cell differentiation.

Animals↗
PubMed1990

Patterns and extent of isotype-specificity in the murine H chain switch DNA rearrangement.

We have analyzed the configuration of the H chain locus of 41 hybridomas by Southern blot analysis. Each H chain switch region was determined to be germ line, rearranged, or deleted. Including 13 previously analyzed hybridomas, 60% of those with rearrangements on both alleles showed a correlation of the two alleles, i.e., both the expressed and the nonexpressed alleles have rearranged to the same H chain constant region gene segment. When the two H chain alleles did not rearrange to the same gene, they often rearranged to neighboring H chain genes. These results support a role for isotype-specific factors in H chain switch recombination. The action of these isotype-specific factors may be propagated to some extent along the chromosome, which would lead to rearrangements to neighboring genes.

Alleles↗
PubMed1989

Products and implied mechanism of H chain switch recombination.

The Ig H chain switch is a DNA recombination event. The recombination occurs between two or more switch regions, areas of tandem sequence duplication that lie upstream of the corresponding H chain C region genes. We have determined the DNA sequence at four recombination sites in three molecularly cloned, rearranged switch regions. All eight donor and recipient recombination sites are at the common pentamers GGGGT, GAGCT, and GGTGG. One of the switch recombination events is an inversion of S gamma 3 sequences. Another of the recombinational events is an internal S gamma 1 deletion, which may be switch enzyme mediated. These results, together with other switch recombination site sequences, suggest that switch recombination is mediated by cutting enzymes with modest specificity and religation enzymes with no specificity.

Base Sequence↗
PubMed1989

T cell leakiness in scid mice.

FACS analysis showed that the incidence of leaky T cells increases with age, such that virtually all old scid mice (greater than 1 year) contain detectable CD3+ cells. The number of detectable T cells remained very low; individual old scid mice generally contained less than 10(5) CD3+ cells. When CD3+ populations in individual leaky mice were analyzed for expression of the T cell subset markers, CD4 and CD8, the ratios of CD4/CD8 were found to be markedly skewed relative to normal mice. This suggested the presence of very few T cell clones. Indeed, the analysis of TCR gene rearrangements in polyclonally stimulated T cell cultures revealed only 1-5 clones in the pooled spleen and lymph nodes of individual old scid mice. These studies also indicated that TCR gene rearrangements in the majority of the stimulated T cell cultures did not contain abnormal J-associated deletions that are characteristic of antigen receptor genes of scid lymphomas. Four of five alloreactive T cell clones from leaky scid mice also apparently lacked abnormal J-associated deletions in their rearranged TCR alleles. Therefore, most leaky lymphocytes appear to derive from progenitors with normal or near-normal scid recombinase activity. However, one of five leaky T cell clones (S1233) and one Con A stimulated monoclonal culture (8706) contained both normally and abnormally rearranged TCR genes. The configuration of TCR loci in such clones may reflect the ability of the defective scid recombinase to mediate normal rearrangements at a low frequency.

Animals↗
PubMed1987

The immunoglobulin heavy chain switch: structural features of gamma 1 recombinant switch regions.

The immunoglobulin heavy chain isotype switch is mediated by a DNA rearrangement involving specific genomic segments referred to as switch regions. Switch regions are composed of tandemly repeated simple sequences. The role of the tandemly repeated structure of switch regions in the switch recombination process is not understood. We mapped eight recombination sites--six in the gamma 1 and two in the gamma 3 tandem arrays. In addition, we obtained molecular clones representing three of the six gamma 1 rearrangements, and determined the nucleotide sequences of the recombination sites in each. In general, the rearrangements are confined to the tandem repeat units, and are not clustered in a particular portion of either the gamma 3 or gamma 1 switch region. Nucleotide sequence analysis of one of the recombinant clones, gamma M35, reveals evidence for a successive switch event wherein a recombination between S mu and S gamma 3 was followed by recombination 57 bp downstream with S gamma 1. gamma 1 sequence data from the molecular clones we obtained, together with similar data from other investigators regarding the gamma 1, gamma 2b, and gamma 2a switch regions, reveals that recombinations tend to occur at homologous positions of the respective gamma-unit repeats, adjacent to the elements AGCT and GGGG found in each. This finding suggests that the cutting and religation step of the recombination process is mediated by a recombinase common to the four gamma-isotypes.

Animals↗
PubMed1987

Palliative bipolar electrocoagulation therapy of obstructing esophageal cancer.

In a multicenter pilot study, a prototype bipolar electrocoagulation tumor probe was employed for palliation of obstructing circumferential esophageal cancer in 20 patients. Mean number of initial treatment sessions was 1.7. Dysphagia and tumor channel size improved significantly after treatment. Mean treatment interval before repeat treatment was 7.6 weeks. Major complications included delayed hemorrhage (two patients) and esophageal-pulmonary fistula (two patients). This new device may provide a less expensive alternative to laser or surgery for palliation of malignant esophageal obstruction.

Adenocarcinoma↗
PubMed1985

Complete nucleotide sequence of the murine gamma 3 switch region and analysis of switch recombination sites in two gamma 3-expressing hybridomas.

The heavy chain isotype switch is mediated by a DNA rearrangement between a donor switch region (usually mu) and a recipient switch region (gamma, epsilon, or alpha). Switch regions lie upstream of the appropriate heavy chain constant region gene and are composed of simple sequences repeated in tandem. It is not known to what extent the tandemly repeated sequences are important to the heavy chain switch recombination, and to what extent other features of switch region sequences might contribute to the switch process. We studied switches to the gamma 3 isotype by sequencing the entire gamma 3 switch region. This switch region is composed of forty-four 49 base pair units repeated in tandem. These repeated units share modest homology with the mu switch region repeated elements. Evolution of the gamma 3 switch region seems to involve insertions and deletions of the 49mer elements. We also molecularly cloned rearranged switch regions from two gamma 3-expressing hybridomas and determined the DNA sequences at the mu-gamma 3 recombination sites. We located these switch recombination sites within the germ-line gamma 3 switch region, as well as switch recombination sites from two myelomas. All four sites are found in the 5' one-third of the gamma 3 switch region. We discuss some additional trends in the sequence data near these four recombination sites.

Animals↗
PubMed1984

Acromegaly and colon cancer.

The occurrence of colon cancer in 1 patient with acromegaly prompted a study of an additional 12 patients with acromegaly. In addition to the index case, 1 patient was retrospectively discovered to have colon cancer, and 1 was found to have colonic adenocarcinoma in the course of the study. One patient had a presumptive sigmoid polyp shown by barium enema but refused further studies. Eight patients received colonoscopy. Two patients had adenomatous polyps and 1 had two hyperplastic polyps. This study supports previously published data on the occurrence of colon polyps in patients with acromegaly and suggests that the incidence of colon cancer is much higher than that expected by chance.

Acromegaly↗
PubMedDate not supplied

The effect of using "race of child" instead of "race of mother" on the black-white gap in infant mortality due to birth defects.

OBJECTIVE: For at least 20 years, birth defects have been the leading cause of infant mortality in the United States. Some studies have reported higher rates for black infants than white infants of mortality due to birth defects, while other studies have reported no black-white differences. The authors analyzed the effect on these rates of a change in the way the National Center for Health Statistics (NCHS) tabulates "race" for newborns. METHODS: The authors calculated infant mortality rates due to birth defects for 1980-1993 using two standard methods of assigning newborns to "racial" categories: a "race of child" algorithm and the "race of mother" approach currently used by NCHS. RESULTS: From 1980 through 1993, birth defect-specific infant mortality rates (BD-IMRs) were significantly higher for black infants than white infants 12 of the 14 years by "race of mother" and only 5 of 14 years by "race of child." Calculation of BD-IMRs by "race of mother" reduced the rate for white infants and increased the rate for black infants in each of the 14 years. The choice of method for assigning newborns to "racial" categories had a progressively greater effect over time on the black-white gap in BD-IMRs. CONCLUSIONS: Calculations of trends in "race"-specific BD-IMRs by may vary substantially by whether "race of mother" or "race of child" is used. Identifying the method of tabulation is imperative for appropriate comparisons and interpretations.

Adult↗