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Biomedical subjects

D L Pittman

Publications and source records attributed to D L Pittman.

At least 19 recordsLinked to original sources
PubMed2000

Midgestation lethality in mice deficient for the RecA-related gene, Rad51d/Rad51l3.

Homologous recombination (HR) occurs in all organisms, and is important for repair of DNA damage, chromosome segregation during meiosis, and genetic diversification. Genes critical for recombinational DNA repair and meiotic recombination include members of the RecA/RAD51 family, of which seven have been identified in mammals. Here, we describe the disruption of Rad51d (recently designated Rad51l3) in mice and its phenotypic consequences. Rad51d-deficient mice die between 8.5 and 11.5 dpc. The affected embryos are smaller than littermates, posteriorly truncated, and developmentally delayed. Embryonic fibroblasts from mutant embryos could not be propagated more than one generation in culture. Rad51d-deficient blastocysts were not sensitive to gamma radiation or methylmethanesulfonate (MMS) in blastocyst outgrowth experiments. The variable and generalized developmental progression defects in Rad51d-deficient embryos suggests that mutant cells may undergo delayed or suboptimal repair of DNA damage, resulting in accumulated degrees of mutation and/or cell cycle perturbation that are incompatible with normal embryonic development. genesis 26:167-173, 2000.

Animals↗
PubMed1998

Identification, characterization, and genetic mapping of Rad51d, a new mouse and human RAD51/RecA-related gene.

Homologous DNA recombination occurs in all organisms and is important for repair of DNA damage during mitosis. One of the critical genes for DNA repair and meiotic recombination in yeast is RAD51, and homologs of RAD51 have been identified in several species, including mouse and human. Here we describe a new RAD51-related mammalian gene, named Rad51d, identified by searching the EST database with the yeast RAD55 and human RAD51B/REC2 genes. A full-length 1.5-kb mouse cDNA clone that encodes a predicted 329-amino-acid protein was isolated. Rad51d mRNA was present in every mouse tissue examined. Four different transcript sizes were detected, one of which was specific to testis. Human cDNA clones that predicted 71% amino acid identity to the mouse protein were also isolated. Interestingly, the sequences of these human clones and of RT-PCR-derived products provided evidence for alternative splicing. These mRNAs are predicted to encode proteins that are truncated relative to the mouse and lack the ATP-binding motif characteristic of RecA-related proteins. Using an interspecific backcross mapping panel, Rad51d was mapped to mouse Chromosome 11, 48.5 cM from the centromere. By radiation hybrid mapping, the human ortholog RAD51D was mapped to chromosome 17q11, which is a region syntenic to mouse Chromosome 11. Due to its expression pattern and sequence similarity to other RAD51 family members, it is likely that Rad51d is part of a complex of proteins required for DNA repair and meiotic recombination.

Amino Acid Sequence↗
PubMed1998

Recombination in the mammalian germ line.

Elucidation of meiotic recombination mechanisms in mammals faces many obstacles. Much of our understanding has been built upon studies in the fungi, which have served to guide experimental design in mammalian cells and mice. A clearer picture is now emerging which reveals that many of the general principles of recombination are conserved across this evolutionary divide. A number of genes critical to meiotic recombination in yeast also exist in mammals. Transgenic technologies, in addition to advances in molecular biology, now provide several strategies to investigate the properties and regulation of mammalian recombination. This chapter reviews the current state of knowledge regarding recombination in the mammalian germ line, covering topics such as gene conversion, recombination mechanics, recombination-based genetic mutation, crossing over, and genes involved in meiotic recombination.

Animals↗
PubMed1998

Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog.

DMC1 is a meiosis-specific gene first discovered in yeast that encodes a protein with homology to RecA and may be component of recombination nodules. Yeast dmc1 mutants are defective in crossing over and synaptonemal complex (SC) formation, and arrest in late prophase of meiosis I. We have generated a null mutation in the Dmc1 gene in mice and show that homozygous mutant males and females are sterile with arrest of gametogenesis in the first meiotic prophase. Chromosomes in mutant spermatocytes fail to synapse, despite the formation of axial elements that are the precursor to the SC. The strong similarity of phenotypes in Dmc1-deficient mice and yeast suggests that meiotic mechanisms have been highly conserved through evolution.

Adenosine Triphosphatases↗
PubMed1997

Examination of the intron in the meiosis-specific recombination gene REC114 in Saccharomyces.

REC114 is one of 10 genes known to be required for the initiation of meiotic recombination in Saccharomyces cerevisiae. It is transcribed only in meiosis, and our previous sequence analysis suggested the presence of an intron in the 3' end of the gene. Hypotheses in the literature have suggested, because of its unusual location, either that the putative intron in REC114 is likely to be necessary for expression, or that there may actually be no intron present. This work demonstrates that REC114 does have an intron and is one of only three genes in yeast with introns located in the 3' end. Furthermore, the 3' splice site utilized in REC114 is a very rare AAG sequence; only three other genes in yeast use this nonconsensus sequence. The splicing of REC114 does not require MER1, a gene known to be involved in meiosis-specific RNA processing. In fact, an intronless copy of REC114 can complement a null rec114 mutation. Thus, it does not appear that the intron is essential for expression of REC114. Although the intron is not absolutely required for meiotic function, it is conserved in evolution; two other species of yeast contain an intron at the same location in their REC114 genes.

Amino Acid Sequence↗
PubMed1996

Analysis of meiotic recombination pathways in the yeast Saccharomyces cerevisiae.

In the yeast, Saccharomyces cerevisiae, several genes appear to act early in meiotic recombination. HOP1 and RED1 have been classified as such early genes. The data in this paper demonstrate that neither a red nor a hop1 mutation can rescue the inviable spores produced by a rad52 spo13 strain; this phenotype helps to distinguish these two genes from other early meiotic recombination genes such as SPO11, REC104, or MEI4. In contrast, either a red1 or a hop1 mutation can rescue a rad50S spo13 strain; this phenotype is similar to that conferred by mutations in the other early recombination genes (e.g., REC104). These two different results can be explained because the data presented here indicate that a rad50S mutation does not diminish meiotic intrachromosomal recombination, similar to the mutant phenotypes conferred by red1 or hop1. Of course, RED1 and HOP1 do act in the normal meiotic interchromosomal recombination pathway; they reduce interchromosomal recombination to approximately 10% of normal levels. We demonstrate that a mutation in a gene (REC104) required for initiation of exchange is completely epistatic to a mutation in RED1. Finally, mutations in either HOP1 or RED1 reduce the number of double-strand breaks observed at the HIS2 meiotic recombination hotspot.

Chromosomes, Fungal↗
PubMed1993

Making sense of coagulation tests, a practical approach.

A large variety of "clotting studies" are available to the clinician in evaluating the hemostatic capability of his patient. The authors have experience with these tests which are available in varying sophistication at hospitals ranging from 25-600 beds. In this article, the biochemistry and physiology of coagulation testing are purposely avoided. A common sense approach to evaluating the patient's "chance of bleeding or clotting" is presented.

Blood Coagulation Tests↗
PubMed1992

Transfusion medicine in the 1990s, why it has changed and how.

This paper is intended for physicians not directly responsible for transfusion medicine in their everyday practices. The field has changed dramatically in the last decade. This paper attempts to outline these changes, and detail factors that will be of practical use in general, medical, and surgical practices. Topics include available blood products with indications and risks, education about types of blood donation, possible future products, and a key concept in the field today, "conservation."

Blood Component Transfusion↗
PubMed1986

Painless giant cell thyroiditis diagnosed by fine needle aspiration and associated with intense thyroidal uptake of gallium.

A 52-year-old woman presented with fever, goiter, and no evidence of pain or tenderness in the thyroid. A diagnosis of silent thyroiditis was made after obtaining evidence of biochemical thyrotoxicosis, intense gallium-67 citrate thyroidal localization, and cytologic thyroiditis. Fine needle aspiration biopsy of the thyroid revealed numerous giant cells in all areas of the thyroid, typical of subacute thyroiditis. This is believed to be the first time painless thyroiditis is reported with the classic cytologic feature of painful subacute thyroiditis.

Biopsy, Needle↗
PubMed1986

Multiple lymphomatous polyposis of the gastrointestinal tract with immunologic marker studies.

We report a rare case of multiple lymphomatous polyposis of the gastrointestinal tract, with emphasis on the radiological, colonoscopic, and morphological findings. The underlying condition proved to be a poorly differentiated lymphocytic lymphoma. This is the first case of multiple lymphomatous polyposis in which immunologic marker studies are described and B cell origin confirmed. The different types of lymphoid polyps of the colon and the role of immunohistology are also discussed.

Aged↗
PubMed1985

Gallium-67 citrate localization in disseminated sporotrichosis.

A 25-year-old woman demonstrated Ga-67 citrate accumulation within a facial cutaneous lesion and two subcutaneous nodules within the right lower extremity. Cultures of the facial lesion and one of the subcutaneous nodules grew Sporothrix schenckii. Ga-67 citrate uptake has not been reported previously with this fungal infection. Ga-67 citrate scintigraphy was helpful in defining the extent of the disease, following its course, and determining the response to therapy.

Adult↗
PubMed1984

Presternal ciliated cyst.

We report the case of a presternal ciliated cyst in a 39-year-old man. The location and histologic features of this lesion have led us to favor a primitive foregut origin for this cyst, probably via the process of embryonic sequestration and migration.

Adult↗
PubMed1982

Effect of chronic non-immunologically mediated bronchoconstriction on bronchial smooth muscle in the guinea pig.

Immature guinea pigs underwent eight weeks of methacholine-induced wheezing on a daily basis. At the end of the study the treated guinea pigs showed less of a weight gain than control animals. Relative dry tracheal weight was greater in the methacholine group than in controls. However, there were no differences noted on histologic examination of the lungs between the treated and control animals. Although experimentally induced amounts of bronchoconstriction may not be extrapolated to the same degree as seen in asthma, these findings suggest that repeated bronchoconstriction alone is not the cause of the smooth muscle hypertrophy and hyperplasia found in asthma.

Animals↗
PubMed1980

Intracranial plasma cell granuloma.

The first case of an intracranial plasma cell granuloma is presented. An associated polyclonal gammopathy was another remarkable feature. Routine and special stains of histologic sections as well as electron microscopy characterized such lesions. Immunofluorescent studies revealed a heterogeneous population of plasma cells. When the granuloma was removed, the polyclonal gammopathy resolved, and neither have recurred with eight months of follow-up. It is suggested that prior reports of meningiomas with conspicuous plasma cell-lymphocytic components may in reality be plasma cell granulomas and could be differentiated by electron microscopy.

Adolescent↗