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Biomedical subjects

M J Murphy

Publications and source records attributed to M J Murphy.

At least 109 records · Page 6Linked to original sources
PubMed1991

Compartmental analysis and glomerular filtration in chick embryos.

We have developed microtechniques that allow the determination of compartmental fluid distribution and glomerular filtration rate in chick embryos during three significant developmental periods: phase 1, the developmental period when the mesonephros alone is functioning; phase 2, periods of simultaneous meso/metanephric kidney function; and phase 3, the period during late development when the metanephros completely replaces the degenerated mesonephros. Water content of tissues is greater in younger embryos (89.4 +/- 0.2%, day 10) compared with older animals (78.3 +/- 0.5%, day 18). Although all major tissue components show an absolute increase in mass during this period, the embryo proper increases at five times the rate of the extraembryonic tissues. Glomerular filtration rate increases during development from 0.61 +/- 0.08 ml/h at day 10 to 2.31 +/- 0.11 ml/h at day 18. Glomerular filtration rate scales to body mass with an allometric exponent identical to adult birds only if total tissue mass (embryo + membranes) is considered. Our data suggest that significant errors in allometry will be encountered when scaling measurements are made on embryonic or fetal amniotes without taking into consideration the extraembryonic tissues.

Animals↗
PubMed1991

Utility of human bone marrow obtained incidental to orthopedic surgery for hematopoietic clonal assays.

We describe the establishment of a convenient method of acquiring human bone marrow cells for use in microcapillary clonal assays. Femoral epiphyseal and diaphyseal bone fragments and femoral canal reamings were collected incidental to total hip replacement surgery and cultured for human granulocyte-macrophage colony-forming units, erythroid burst-forming units and erythroid colony-forming units. This readily available source of normal human marrow provides an abundant quantity of hematopoietic progenitors of documented normalcy.

Adult↗
PubMed1991

Elevated 25-hydroxy and normal 1,25-dihydroxy cholecalciferol serum concentrations in a successfully-treated case of vitamin D3 toxicosis in a dog.

A 4-y old, 27 kg spayed female German Shepherd dog was observed to ingest one 1-oz package of a rodenticide containing cholecalciferol. An initial serum calcium concentration of 15.7 mg/dl was successfully reduced to normal during 10 d using calcitonin and prednisolone. During that time, the serum 25-hydroxy and 1,25-dihydroxy cholecalciferol concentrations ranged from 637 to 315 ng/ml (normal 32 +/- 6 ng/ml) and 64 to 29 pg/ml (normal 34 +/- 19 pg/ml), respectively. Serum mid-molecule parathyroid hormone concentrations (76 to 97 pcmol/L) were within the normal range (85-140 pcmol/L). These data indicate that hypercalcemia seen in dogs following field exposures to cholecalciferol-containing rodenticides may be associated with elevated 25-hydroxy rather than 1,25-dihydroxy cholecalciferol. Consequently, serum 25-hydroxy cholecalciferol concentrations may be the most conclusive method for diagnosing hypervitaminosis D3 toxicosis in the live dog.

Animals↗
PubMed1990

Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of three cases.

The vitamin K metabolism of three patients with factitious purpura due to brodifacoum ingestion was studied. These patients, who presented with bleeding disorders due to deficiency of the vitamin K-dependent blood clotting proteins, were refractory to vitamin K1 at standard doses and required fresh frozen plasma to control bleeding until large doses of vitamin K1 were used. Metabolic studies demonstrated a blockade in vitamin K utilization, consistent with the presence of a vitamin K antagonist, but the patients denied use of anticoagulants. Warfarin assays were negative. We show that the factitious purpura in each patient was due to the surreptitious ingestion of brodifacoum, a potent second generation long-acting vitamin K antagonist used as a rodenticide. The coagulopathies responded to long-term therapy with large doses of vitamin K1. The serum elimination half-time for brodifacoum ranged from 16 to 36 days in these patients. The anticoagulant effect is of long duration, requiring chronic vitamin K treatment. With increasing availability of new rodenticides, factitious purpura due to surreptitious ingestion of these potent vitamin K antagonists is emerging as a new problem, previously associated with warfarin, with important implications for diagnosis and treatment.

4-Hydroxycoumarins↗
PubMed1990

Enhanced expression of ganglioside GD3 in human and rat hepatocellular carcinoma cells and NIH 3T3 cells transfected with human tumor DNAs.

The gangliosides of human hepatoma biopsies, human hepatoma cell lines, and diethylnitrosamine-induced rat hepatomas were examined. These malignant tissues all expressed increased content of disialolactosylceramide (GD3) with respect to their normal counterparts. During the induction of rat hepatoma by diethylnitrosamine, an increase in GD3 levels appeared as early as 12 wk after initiation of diethylnitrosamine, concurrent with the appearance of precancerous hepatocytes. GD3 levels gradually increased to a peak of 4 times that of normal rat liver at 20 wk. CMP-NeuAc:GM3 sialyltransferase, the enzyme that synthesizes GD3 by transfer of sialic acid to GM3, also had tumor-associated elevation during the course of diethylnitrosamine-induction of rat hepatomas. To investigate the relationship of oncogene transformation and changes in ganglioside biosynthesis, NIH 3T3 cells transfected DNAs from human hepatoma or nasopharyngeal carcinoma were studied. The transfectants each expressed the same ganglioside composition, including a detectable level of GD3, as well as enhanced activity of CMP-NeuAc:GM3 sialyltransferase. A correlation between the tumor DNA transfection and the augmentation of GD3 in malignant cells is discussed. Because of the early appearance of GD3 in hepatoma and its possible relationship to oncogene activation, GD3 may be a potentially useful early tumor marker.

Animals↗
PubMed1990

Effects of L-phenylalanine mustard and L-buthionine sulfoximine on murine and human hematopoietic progenitor cells in vitro.

The effects of L-buthionine sulfoximine (L-BSO) and L-phenylalanine mustard (L-PAM), alone and in combination, on human and murine marrow were explored using in vitro clonogenic assays to establish whether enhanced myelotoxicity might limit the clinical utility of this potent chemotherapeutic combination. One-h exposure to L-PAM produced significant concentration-dependent colony inhibition, with 70% inhibitory concentration (IC70) values ranging from 4.5 to 7.2 microM for all hematopoietic progenitors assayed. The combination of L-PAM plus 4500 microM L-BSO for 1 h did not effectively alter the IC70 values derived for L-PAM alone. In studies where marrow cells were pretreated with L-BSO for 4 h and then L-PAM for 1 additional h, the IC70 values were decreased in both murine and human marrow progenitors compared to the L-PAM control, suggesting modest potentiation of myelotoxicity. The potentiation is not so significant as to preclude human studies with this combination. One- to 5-h exposure of marrow cells from both species to 4500 microM L-BSO was only mildly myelotoxic, producing colony reductions of 22-49%. However, continuous exposure to L-BSO produced concentration-dependent colony inhibition, with IC70 values of 70, 84, and 43 microM for murine colony-forming units-granulocyte/macrophage, blast-forming units-erythroid, and colony-forming unit-erythroid, respectively.

Animals↗
PubMed1990

The avian embryo as a model for early developmental endocrinology.

Studies utilizing the developing chicken embryo have significantly augmented our understanding of the ontogeny of endocrine regulation during major critical periods of embryonic development. These embryos currently provide the only available models for elucidating the onset of endocrine function during all stages of in situ amniote development, for examining chronic calcium deficiency during embryogenesis, and for experiments in basic renal function during periods when only the mesonephros is normally functioning, as well as mixed meso/metanephric function and solely metanephric kidney function.

Animals↗
PubMed1990

Partial purification and characterization of human megakaryocyte colony-stimulating factor (Meg-CSF).

Megakaryocyte colony-stimulating factor (Meg-CSF) in urinary extracts from patients with aplastic anemia was partially characterized and purified. Using Meg-CSF-enriched fractions, we established that the moiety has the following characteristics: 1) portions of the molecules having Meg-CSF activity have sialic acid, probably with a biantennary structure, and beta-galactose residues as the terminal and penultimate sugars; 2) disulfide residues are an essential chemical group of the molecule and are located on its surface; and 3) Meg-CSF activity is stable in n-propanol, but not in acetonitrile with trifluoroacetic acid. Partial purification of Meg-CSF by a four-step procedure of ethanol precipitation, CM Affi-Gel Blue chromatography, wheat germ agglutinin-sepharose chromatography, and high-resolution hydroxyapatite chromatography, yielded a concentrate with a 430- to 630-fold increase in specific activity. The partially purified Meg-CSF fractions stimulated both human and murine megakaryocytopoiesis in vitro (CFU-meg). When analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreduced conditions, Meg-CSF activity was recovered in the 29-34 kDa molecular weight fractions. We have also shown that Meg-CSF, purified from the urine of aplastic anemia patients, stimulated murine megakaryocytopoiesis and platelet production in vivo. Final purification of human urinary Meg-CSF is currently in progress.

Anemia, Aplastic↗
PubMed1990

Q-switched ruby laser treatment of tattoos; a 9-year experience.

Nine years of clinical experience of the application of the Q-switched ruby laser to the removal of tattoos is presented. This laser achieves optimal removal of blue/black amateur tattoos by its selective interaction with the dermal suspensions of pigment which constitute the tattoos. The scar free cosmesis thus achieved is a considerable improvement on non-specific laser techniques whereby the laser is absorbed to a comparable degree in both pigmented and non-pigmented tissue. Long-term results are analysed and it is noted that a variety of professional tattoos may also respond to treatment. The mechanisms and appearance are discussed and correlated with short-term healing processes. It is found that power densities in the range 1200-2800 GW/m2 are most suitable. Appropriate dosimetry can be witnessed by the appearance of opaque intradermal vacuoles corresponding to the vaporization of the tissue water surrounding the pigment suspensions. Treatment by Q-switched ruby laser offers a viable scar-free option for a wide range of dark tattoos, leading to a more acceptable clinical outcome in most cases than other current therapies.

Dermatologic Surgical Procedures↗
PubMed1990

Extensive wounds of the spine: a comprehensive approach to debridement and reconstruction.

Extensive wounds involving the spine (greater than three vertebral segments exposed) may threaten its indispensable roles of biomechanical support and vital neurologic function. Although there have been select reports of specific flap applications in this body region in the reconstructive surgical literature, there has been a paucity of comprehensive descriptions of pertinent anatomy, pathophysiology, and the perioperative care of such patients--including the degree to which the spine is suited to aggressive debridement. Four patients with complex spine wounds involving greater than three vertebral segments were treated by the authors from 1986 through 1988. These patients ranged from 28 to 80 years of age. They were all found to have multiple risk factors, including neoplasm (4), severe nutritional depletion (3), advanced age (2), wound sepsis (2), and multiple other general medical problems (4). All patients underwent wide bony and soft-tissue debridement. A new clinically essential four-pillar concept of spinal support predicted spinal instability in two of the four patients. These patients could thus be protected from neurologic compromise with internal stabilization (1) or external orthotic support (1). Wound closure was achieved with skin graft (1) or traditional or extended musculocutaneous flap coverage (3). With 7 to 20 months of follow-up, wound healing has been complete in all patients despite a 100 percent complication rate and one late postoperative death. Multisegment spine wounds tend to arise in the setting of multiple medical problems or risk factors. Despite these risk factors and a high postoperative complication rate, gratifying results may be achieved in these patients with a comprehensive understanding of regional surgical anatomy and a multidisciplinary approach to their care.

Adult↗
PubMed1990

Cloning of primary human tumors in capillary tube versus Petri dish: a head-to-head comparison.

Plating efficiencies (PEs) of primary human tumors cloned in a capillary assay system were compared to those derived from the conventional two-layer agar Petri dish assay system. A total of 143 consecutively received primary human tumors of 24 different pathologies were simultaneously tested in both assay systems. The successful clonal growth rate in the capillary assay was 82.7%, while in the Petri dish it was 64.7% (p less than 0.001). The median PE was 0.017% in the capillary assay demonstrating a 4.25-fold increase over the 0.004% PE of the Petri dish system. The data confirmed previous results showing that cancer cells of ovarian, breast, and lung origins clone with higher PE in capillary tubes. In contrast, we confirmed that stomach carcinoma cells were the only tumor type that showed a higher PE with the Petri dish method. In addition, this study shows for the first time that lymphomas and renal cell carcinoma, when they survive in vitro, clone equally well in both methods. However, the capillary cloning method resulted in a 66% success rate for lymphoma cell cloning, but Petri dish cloning resulted in only a 33% success rate. Thus, for some types of cancers (i.e., lymphoma), capillary cloning may be advantageous because it improves the probability of obtaining evaluable results. In other cases, the advantage of capillary cloning may be only the decreased amount of specimen and reagents needed for the assay.

Cell Biology↗
PubMed1990

Determinants of elevated blood lead during pregnancy in a population surrounding a lead smelter in Kosovo, Yugoslavia.

We are prospectively examining the relation between environmental lead exposure and pregnancy outcome in cohorts of women exposed to a wide range of air lead concentrations. Titova Mitrovica, Yugoslavia, is the site of a large lead smelter, refinery, and battery factory. At midpregnancy, 602 women in T. Mitrovica and 900 women in Pristina, a non-lead-exposed control town, were interviewed. Blood was obtained for blood lead (PbB), hemoglobin, erythrocyte protoporphyrin, and serum ferritin measurements. Women were seen again at delivery, at which time maternal and umbilical cord blood samples were obtained. While many demographic and social characteristics were similar across the two towns, women in Pristina were more likely to report employment outside the home, cigarette smoking, and alcohol use during pregnancy. As expected, PbB levels were substantially higher in the smelter town. At midpregnancy, PbB geometric means were 17.1 micrograms/dL in T. Mitrovica and 5.1 micrograms/dL in Pristina; 86% of the pregnant women in T. Mitrovica, compared to 3.4% of those in Pristina, had PbB levels greater than 10 micrograms/dL. Within T. Mitrovica, distance between the home and the smelter was the most important predictor of PbB at mid-pregnancy and delivery. Husband's employment in the lead industry was associated with a significant increase in maternal PbB levels independent of place of residence. Higher maternal serum ferritin concentrations were associated with lower PbB levels, suggesting that dietary iron inhibits lead absorption. Overall, the placenta was a poor barrier to lead; the relationship between maternal PbB and umbilical cord PbB was linear across a wide range of PbB levels.

Adult↗
PubMed1990

Past pregnancy outcomes among women living in the vicinity of a lead smelter in Kosovo, Yugoslavia.

This analysis compares the rates of spontaneous abortion among women living in the vicinity of a lead smelter with those of women living in a town where blood lead levels were low. Data derive from the obstetric histories of both groups of women obtained while seeking prenatal care for a later pregnancy. A total of 639 women (304 exposed, 335 unexposed) had at least one previous pregnancy and lived at the same address since their first pregnancy. The geometric mean blood lead concentrations in the sample at the time of the interviews were 0.77 mumol/L in the exposed town and 0.25 mumol/L in the unexposed town. The rates of spontaneous abortions in first pregnancies were similar, with 16.4 percent of women in the exposed town and 14.0 percent in the unexposed town reporting loss. The adjusted odds ratio relating town of residence to spontaneous abortion was 1.1 (95% CI = 0.9, 1.4). This analysis represents the first systematic attempt to seek an association between environmental lead exposure and spontaneous abortion. As such, the failure to find a positive association strongly suggests that at the levels of exposure represented in our sample, such an association does not exist.

Abortion, Spontaneous↗
PubMed1990

In vitro myelotoxicity of 2',3'-dideoxynucleosides on human hematopoietic progenitor cells.

Three nucleoside analogues, 2',3'-dideoxyadenosine (ddA), 2',3'-dideoxyinosine (ddI), and 2',3'-dideoxycytosine (ddC), were evaluated for their potential myelotoxic effects to normal human hematopoietic progenitor cells. The myeloid (granulocyte-monocyte colony-forming units, CFU-gm) and erythroid (erythroid burst-forming units, BFU-e: and erythroid colony-forming units, CFU-e) committed progenitor cells were exposed to the agents for a 1-h period prior to culture in a microcapillary assay or continuously exposed during the entire culture period. Both ddA and ddI (100 microM) were mildly toxic (less than 50% colony inhibition) to human CFU-gm, BFU-e, and CFU-e following either 1-h or continuous exposures. Marrow progenitor sensitivities to ddA and ddI were indistinguishable. Colony inhibition ranged from 47% to 67% for 1-h ddC exposure (100 microM), values that were comparable to ddA and ddI. Continuous exposure to ddC was highly myelotoxic to human hematopoietic progenitors, with concentrations of 10 and 100 microM suppressing colony formation by 79%-92% and 93%-97%, respectively. These results demonstrate that 1-h and continuous exposures to ddA and ddI were similarly myelotoxic to human hematopoietic cells, whereas a 1-h exposure to ddC was equivalent to ddA and ddI, yet continuous ddC exposure was extremely toxic to marrow cell progenitors.

Bone Marrow↗
PubMed1989

Capillary cloning of primary human tumor cells: assay miniaturization for drug efficacy testing.

The conventional double-layer agar method of cloning human tumor cells requires a substantial number of viable tumor cells and 14-21 days of culture. These prerequisites frequently limit its utility as an assay. In an attempt to circumvent these limitations and to reduce the amount of drug that is needed in the assay, we have further developed and miniaturized the assay in which human tumor cells are cloned in glass microcapillary tubes. Cultures consisted of 50 microliters containing 15,000 nucleated cells in 975 mm capillary tubes which were incubated for seven days. The results from 50 consecutive tumor biopsies resulted in cloning efficiencies, ranging from 0.007% to 1.0% with an overall successful cloning of 88% of all tumors tested and a good linear growth relationship and chemotherapy sensitivity. This miniaturized assay offers distinct advantages for drug efficacy testing including high cloning efficiencies, small tumor sample and drug requirements, quicker assay turnaround time and a general conservancy of reagents and incubator space.

Antineoplastic Agents↗