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L L Peters

Publications and source records attributed to L L Peters.

At least 55 records · Page 3Linked to original sources
PubMed1993

Distinct fetal Ank-1 and Ank-2 related proteins and mRNAs in normal and nb/nb mice.

Mice homozygous for the mutation normoblastosis (gene symbol nb on chromosome 8) are deficient in erythroid ankyrin (ANK-1) and have a severe hemolytic anemia throughout life. Characteristic of the disease is a dramatic decrease in the level of expression of the Ank-1 gene (chromosome 8). The other major ankyrin transcript, brain ankyrin (Ank-2 on chromosome 3) is expressed at normal levels in nb/nb mice. Surprisingly, nb/nb fetuses have normal erythrocyte counts despite the decreased levels of Ank-1 transcripts. We previously hypothesized that fetal-specific ankyrin-related proteins could exist in nb/nb fetuses to account for the lack of detrimental effects of ANK-1 deficiency. In the present report, Western and Northern blot analyses were performed on hematopoietic cells isolated from nb/nb and +/+ fetuses. An ANK-1-related protein (165 Kd) in fetal reticulocytes persisted in adult nb/nb but not in +/+ reticulocytes. An Ank-1-related transcript of 5.5 kb was found in fetal reticulocytes. This transcript appeared to be upregulated in nb/nb but not in +/+ adult reticulocytes. A fetal-specific ANK-2-related protein (155 Kd) was present in nb/nb and in +/+ fetal reticulocytes. Ank-2-related fetal liver mRNAs were present during the time the liver was actively generating erythrocytes. Neither the Ank-2-related transcripts nor the 155-Kd ANK-2-related protein were found in +/+ or mutant adult reticulocytes. The data indicate that (1) unique ankyrin-related proteins and mRNAs present in fetal erythrocytes may stabilize the ankyrin-deficient nb/nb erythrocytes and (2) adult nb/nb mice may upregulate fetal gene transcripts to compensate for the ANK-1 deficiency.

Anemia, Hemolytic↗
PubMed1992

Fetal compensation of the hemolytic anemia in mice homozygous for the normoblastosis (nb) mutation.

The mouse autosomal recessive mutation nb causes a deficiency of erythroid ankyrin and generates a life-threatening hemolytic anemia in adult mice; however, at birth, nb/nb mice appear to be robust and show no pallor. In our study, the time of disease onset was sought by comparison of nb/nb and +/? mice both in utero and postnatally. Erythroid ankyrin messenger RNA (mRNA) is expressed in fetal erythroid progenitors from normal mice, but is reduced to 10% of normal levels in mutant fetuses. Despite the deficiency of erythroid ankyrin mRNA, 16 and 18 day nb/nb fetuses have normal levels of red blood cells (RBCs) and the RBCs are morphologically normal by scanning electron microscopy. The earliest signs of any clinical anomaly are an increase in the number of circulating reticulocytes and the deposition of minor amounts of iron just before birth in the 18 day fetal nb/nb liver, suggesting that RBCs are being destroyed. Within 24 hours after birth, nb/nb neonates have a slight but significant decrease of their RBC counts. During the next 5 days, the nb/nb RBC counts decrease markedly, the reticulocyte counts assume the mutant adult levels of 60%, the erythrocytes become microcytic and fragmented, and iron deposits accumulate in the liver. The rapid onset of clinical disease postnatally, coupled with our findings that the erythroid ankyrin gene is transcribed in fetal erythroid cell precursors from normal mice, suggest that mechanisms exist in the nb/nb fetus to compensate for the erythroid ankyrin deficiency.

Aging↗
PubMed1992

Changing patterns in cytoskeletal mRNA expression and protein synthesis during murine erythropoiesis in vivo.

The major cytoskeletal proteins alpha-spectrin, beta-spectrin, and ankyrin are synthesized and assembled into a supportive membrane skeleton during erythroid differentiation. Information on the temporal appearance of mRNA and protein species is essential for understanding both the cytoskeletal assembly process and the function of various isoforms. We have isolated highly enriched populations of fetal erythroid cells at various stages of maturation. mRNAs for erythroid ankyrin, alpha-spectrin, and beta-spectrin were expressed at all stages but there were differences in transcript types and levels. The ratio of 9-kilobase (kb) to 7.5-kb erythroid ankyrin transcripts decreased markedly during differentiation, but there was no change in the ratio of the 10.1-kb and 9.3-kb erythroid beta-spectrin transcripts. The relative amounts of ankyrin, alpha-spectrin, and beta-spectrin mRNA increased during yolk sac cell differentiation, whereas only alpha-spectrin mRNA increased during differentiation of the fetal liver cells. The amounts of beta-spectrin mRNA exceeded the amounts of alpha-spectrin mRNA in the early precursors from both yolk sac and fetal liver; protein synthetic levels showed the same pattern. The 16-day fetal peripheral reticulocytes, on the other hand, had the adult mRNA and protein synthetic ratios with alpha/beta greater than 1. The data indicate that at least two mechanisms exist to meet changing erythroid membrane cytoskeletal requirements during development in utero: (i) stage-specific processing of the mRNA for the major cytoskeletal linker protein ankyrin and (ii) developmentally regulated alpha/beta-spectrin protein synthetic rates.

Animals↗
PubMed1992

Murine erythrocyte ankyrin cDNA: highly conserved regions of the regulatory domain.

Ankyrin is an essential link between cytoskeletal proteins, such as spectrin, and membrane bound proteins, such as protein 3, the erythrocyte anion exchanger. Although the amino acid structure of human ankyrin is known, the functional regions have been only partially defined. Sequence comparisons between mouse and human ankyrin offer one mechanism of identifying highly conserved regions that probably have functional significance. We report the isolation and sequencing of a series of overlapping murine erythroid ankyrin (Ank-1) cDNAs from spleen and reticulocyte libraries (total span 6238 bp) and identify potentially important regions of murine-human reticulocyte ankyrin homology. Comparison of the predicted peptide sequences of mouse and human erythroid ankyrins shows that these ankyrins are highly conserved in both the N-terminal, protein 3 binding domain (96% amino acid identity) and in the central spectrin-binding domain (97% identity), but differ in the C-terminal regulatory domain (79% identity). However, the C-terminal regulatory domain contains two regions of peptide sequence that are perfectly conserved. We postulate these regions are important in the regulatory functions of this domain.

Amino Acid Sequence↗
PubMed1992

The murine pallid mutation is a platelet storage pool disease associated with the protein 4.2 (pallidin) gene.

Pallid is one of 12 independent murine mutations with a prolonged bleeding time that are models for human platelet storage pool deficiencies in which several intracellular organelles are abnormal. We have mapped the murine gene for protein 4.2 (Epb4.2) to chromosome 2 where it co-localizes with pallid. Southern blot analyses suggest that pallid is a mutation in the Epb4.2 gene. Northern blot analyses demonstrate a smaller than normal Epb4.2 transcript in affected pallid tissues, such as kidney and skin. This is the first gene defect to be associated with a platelet storage pool deficiency, and may allow the identification of a novel structure or biological pathway that influences granulogenesis.

Animals↗
PubMed1991

Purkinje cell degeneration associated with erythroid ankyrin deficiency in nb/nb mice.

Mice homozygous for the nb mutation (Chromosome 8) have a severe hemolytic anemia and develop a psychomotor disorder at 6 mo of age. The nb/nb mice are deficient in erythroid ankyrin (Ank-1) but, until the present study, the role of Ank-1 and of Ank-2 (brain ankyrin) in disease genesis was unknown. In normal erythroid tissues, we show that two major transcripts are expressed from Ank-1, and one of these is also present at high levels in the cerebellum. By in situ hybridization and immunocytochemistry, Ank-1 localizes to the cerebellar Purkinje cells and, to a lesser extent, the granule cells. In nb/nb mice, Ank-1 transcripts are markedly reduced in both erythroid and neural tissue, and nb/nb Purkinje cells and granule cells are nearly devoid of Ank-1. The neurological syndrome appears concurrently with a dramatic loss of Purkinje cells. Ank-2 maps to Chromosome 3 and its expression is unaffected by the nb mutation. We conclude that Ank-1 is specifically required for Purkinje cell stability and, in its absence, Purkinje cell loss and neurological symptoms appear.

Anemia, Hemolytic↗
PubMed1990

Heritable severe combined anemia and thrombocytopenia in the mouse: description of the disease and successful therapy.

A new autosomal recessive mouse mutation, scat (severe combined anemia and thrombocytopenia), causes intermittent episodes of severe bleeding in the homozygote. At birth, affected mice are pale with intradermal petechiae and bruises on exposed surfaces. Central nervous system (CNS) bleeding occurs in 22% of the mice. Gastrointestinal (GI) hemorrhaging and splenomegaly are noted in moribund mice at autopsy. Of the 291 mice studied, 113 mice survived the initial crisis and entered a spontaneous remission period lasting from day 16 to day 27. A second crisis period ensued, and all but 22 mice died by 45 days. Mice in crisis show significantly decreased platelets, erythrocytes, and leukocytes and increased reticulocytes when compared to normal littermates. During remission all parameters are significantly improved or revert to normal values. Neither splenomegaly nor internal bleeding are observed during remission. A platelet-specific antibody is present in the plasma of mutant mice during crisis. The symptoms (severe bleeding, anemia, low-platelet counts) and platelet-specific antibody production are transferred to lethally irradiated normal mice through spleen cell transplantation. Splenectomy of mice in remission significantly increases survival. Exploitation of the features common to both scat/scat mice and patients with some forms of autoimmune thrombocytopenic purpura will undoubtedly prove useful in defining common pathways of disease development and in testing potential therapeutic measures.

Anemia↗
PubMed1989

Pituitary intracisternal granule formation during the estrus cycle of the rat.

An ultrastructural study of the anterior pituitaries of cycling rats reveals changes in the ultrastructure of the gonadotrophs during the afternoon of proestrus when the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) is high. The rough endoplasmic reticulum cisternae become greatly dilated, forming extensive channels which are continuous with the perivascular space and provide an increased surface for the release of hormones. Granules and cytoplasmic islands of granules are seen in these spaces. Such changes are not observed during diestrus and early proestrus when the release of FSH/LH is low. The data indicate that intracisternal granule formation is an important mechanism by which anterior pituitary cells respond to increased hormonal requirements.

Animals↗
PubMed1987

The prenatal development of the organ of Zuckerkandl in rats.

The effect of maternal glucocorticoid depletion upon the fetal development of the organ of Zuckerkandl (OZ) in rats was determined. Maternal hypophysectomy at 13d8h gestation resulted in a fifty percent decrease in plasma corticosterone levels at 18d8h when compared to both sham operated and unoperated controls. No differences in the volume of the OZ among the three groups of animals were found. The chromaffinity of the OZ was decreased in the hypophysectomized and sham operated groups suggesting a stress-induced depletion of catecholamine stores. The data suggests that the OZ participates in fetal sympathoadrenal activity and that its development is independent of maternal corticosterone titers.

Animals↗
PubMed1987

Evaluation of patient-specific computer-generated drug information monographs.

A computerized Medication Awareness Reporting System (MARS) generated by a Sperry PC microcomputer with an Epson FX-80+ printer was evaluated on four adult units (163 beds) of a 353-bed community hospital. MARS is a drug database containing clinical information monographs on 200 commonly prescribed medications. Information provided through the MARS system includes mechanism of action, dosage and administration guidelines, adverse effects and contraindications. In addition, pharmacists can add written information to each MARS report. Patient-specific MARS reports were generated on all patients admitted to the four units during the 16-week study period. Copies of the reports were placed into each patient's chart and into the patient's medication Kardex. Reports were updated daily by pharmacists who provide decentralized service to the units. Physicians, pharmacists, and nurses who encountered the MARS reports were surveyed at the end of the 16-week period. The results indicated that nurses used MARS more than physicians or pharmacists. The groups that valued the MARS reports as a source of drug information the least were the pharmacists and the physicians. MARS, or a drug information system similar to MARS, can be provided with relatively little cost for equipment and materials. However, the use of MARS as described in this study may be limited due to the time required to provide this service. More efficient methods of delivering MARS may enhance its use in the hospital setting. Currently, MARS may be more appropriate for use in long-term care facilities and home health agencies.

Attitude of Health Personnel↗
PubMed1982

Posterior pituitary lobectomy: differential elevation of plasma prolactin and luteinizing hormone in estrous and lactating rats.

The effects of posterior pituitary lobectomy on PRL and LH secretion in estrous and lactating rats were examined. Blood was collected from a femoral artery immediately before and at various times after the removal of the posterior lobe from anesthetized rats. Rats in estrus were also subjected to chronic posterior lobectomy, and their water consumption and vaginal cytology were determined for 3 weeks. Within 5--10 min after posterior lobectomy in estrous rats, plasma PRL increased 3-fold, but declined to near control levels by 1--2 h. Plasma LH increased more gradually, reaching 4 times the control level after 2--3 h. No change was observed in plasma GH. Injection of dopamine to posterior lobectomized estrous rats caused an immediate fall in plasma PRL, but no change in LH. Plasma PRL in lactating rats increased 4-fold after posterior lobectomy, reaching a peak concentration by 30 min and remaining elevated for at least 3 h; plasma LH was unchanged. Eighty percent of chronic posterior lobectomized rats became pseudopregnant and then resumed normal cyclicity. Water consumption increased 3-fold after posterior lobectomy, but declined to 60--70% above the control level after 2--3 weeks. The data suggest that the posterior lobe participates in the regulation of PRL secretion via a dopaminergic mechanism; such regulation might be more pronounced during lactation than in estrus. In addition, the posterior pituitary appears to contribute to the regulation of LH secretion during estrus. The factor(s) of posterior pituitary origin responsible for inhibiting LH secretion is unknown at the present time.

Animals↗
PubMed1981

The posterior pituitary: regulation of anterior pituitary prolactin secretion.

Removal of the posterior pituitary from anesthetized male rats results in a prompt and significant increase in circulating prolactin that is reversed by the injection of dopamine. Posterior pituitary extracts, which contain high concentrations of endogenous dopamine, inhibit prolactin secretion from isolated anterior pituitary cells. This inhibition is prevented by incubation of the cells with the dopamine receptor antagonist (+)-butaclamol. The data show that posterior pituitary dopamine reaches the anterior pituitary via the short hypophysial portal vessels and participates in the regulation of prolactin secretion.

Animals↗