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Biomedical subjects

M R Smith

Publications and source records attributed to M R Smith.

At least 91 records · Page 5Linked to original sources
PubMed1996

Lead exposure in Laysan albatross adults and chicks in Hawaii: prevalence, risk factors, and biochemical effects.

Prevalence of lead exposure and elevated tissue lead was determined in Laysan albatross (Diomedea immutabilis) in Hawaii. The relationship between lead exposure and proximity to buildings, between elevated blood lead and droopwing status, and elevated liver lead and presence of lead-containing paint chips in the proventriculus in albatross chicks was also examined. Finally, the effects of lead on the enzyme delta-aminolevulinic acid dehydratase (ALAD) was determined. There was a significant association between lead exposure or elevated tissue lead and proximity to buildings in albatross chicks and presence of lead paint chips in the proventriculus and elevated liver lead in carcasses. Although there was a significant association between elevated blood lead and droopwing chicks, there were notable exceptions. Prevalence of elevated tissue lead in albatross chicks was highest on Sand Island Midway and much less so on Kauai and virtually nonexistent in other areas. Prevalence of lead exposure decreased as numbers of buildings to which chicks were exposed on a given island decreased. Laysan albatross adults had minimal to no lead exposure. There was a significant negative correlation between blood lead concentration and ALAD activity in chicks. Based on ALAD activity, 0.03-0.05 microg/ml was the no effect range for blood lead in albatross chicks.

Aging↗
PubMed1996

Mammalian evolution and the interphotoreceptor retinoid binding protein (IRBP) gene: convincing evidence for several superordinal clades.

Phylogenetic relationships of 25 mammalian species representing 17 of the 18 eutherian orders were examined using DNA sequences from a 1.2-kb region of the 5' end of exon 1 of the single-copy nuclear gene known as interphotoreceptor retinoid binding protein (IRBP). A wide variety of methods of analysis of the DNA sequence, and of the translated products, all supported a five-order clade consisting of elephant shrew (Macroscelidea)/aardvark (Tubulidentata)/and the paenungulates (hyracoids, sirenians, and elephants), with bootstrap support in all cases of 100%. The Paenungulata was also strongly supported by these IRBP data. In the majority of analyses this monophyletic five-order grouping was the first branch off the tree after the Edentata. These results are highly congruent with two other recent sources of molecular data. Another superordinal grouping, with similar 100% bootstrap support in all of the same wide-ranging types of analyses, was Artiodactyla/Cetacea. Other superordinal affinities, suggested by the analyses, but with less convincing support, included a Perissodactyla/Artiodactyla/Cetacea clade, an Insectivora/Chiroptera clade, and Glires (an association of rodents and lagomorphs).

Animals↗
PubMed1996

Clonal evolution of chronic lymphocytic leukemia to acute lymphoblastic leukemia.

A 38-year-old white man was diagnosed with B-cell chronic lymphocytic/prolymphocytic leukemia (CLL/PLL). The disease was unresponsive to a variety of chemotherapeutic regimes. One year after diagnosis, L3 blasts appeared in peripheral blood associated with more aggressive course. There was no change in the B-cell phenotype at that time, but cytogenetic analysis revealed the appearance of t(8;22)(q24;q11) and -21 superimposed on the original karyotype: 46,XY,+3,der(3)t(3;17)(p11;q12), t(11;14)(q13;q32),-17. These results indicate that the lymphoblastic transformation in our case emerged from the pre-existing B-lymphocytic clone.

Adult↗
PubMed1996

Thymosin alpha 1 does not promote growth or oncogenic transformation.

Thymosin alpha 1 (T alpha 1) is an immune modulatory peptide which has been evaluated in a variety of clinical trials. Although no in vivo adverse effects, including enhancement of tumor growth, have been noted, in vitro studies suggesting a role for T alpha 1 in cell growth have been reported. The studies presented in this report evaluated both exogenously added T alpha 1 and endogenously expressed T alpha 1 as factors which could either promote growth of tumor cells or induce transformation. No effect of exogenous T alpha 1 on cell growth was found. NIH-3T3 cells transfected with cDNA for the precursor ProThymosin alpha (Pro T alpha) expressed elevated levels of authentic T alpha 1 but did not demonstrate either enhanced proliferation in liquid culture or transformation as defined by the loss of contact inhibition or anchorage independent growth in soft agar. Thus these studies argue against the hypothesis that T alpha 1 is either an intracellular or extracellular growth promoter.

3T3 Cells↗
PubMed1996

Hematology for primary care physicians.

Many hematologic disorders present minimal physical signs and symptoms in the early state. For example, chronic myelogenous leukemia may not manifest splenomegaly or any obvious physical signs, yet the laboratory report may demonstrate leukocytosis, eosinophilia, basophilia, and thrombocytosis. Although the anemic condition of a patient with a hemoglobin level of 7 gm/dl may be readily apparent to the clinician, a hemoglobin level of 10.5 gm/dl may be difficult to discern during a brief visit that is focused on another organ system. The same laboratory report, however, may contain valuable clues about unsuspected anemia related to mean corpuscular volume or morphology. Information from supporting chemistry studies often may be helpful in interpretation of the diagnosis. An elevated uric acid level, for example, may indicate hyperkinetic cytogenesis related to myeloproliferative or lymphoproliferative neoplastic disorders. This monograph is designed to be useful to busy physicians who want to use basic hematologic studies in a cost-effective manner. Hematology is viewed in a problem-oriented way; the laboratory report is used as the problem generator.

Anemia↗
PubMed1996

Suppression of in vivo tumor growth and induction of suspension cell death by tissue inhibitor of metalloproteinases (TIMP)-3.

Tissue inhibitor of metalloproteinases-3(TIMP-3), a novel member of TIMP family genes, has been recently cloned and shown to be expressed in preneoplastic but not in neoplastic mouse JB6 epidermal cells (Sun et al. 1994 Cancer Res., 54, 11139). This down regulation of the gene appears to be attributable at least in part to alteration of gene methylation (Sun et al. 1995 J. Biol. Chem., 270, 19312). Little is known, however, about the role of TIMP-3 in human cancers. We screened several human tumor cell lines for TIMP-3 expression and found that a colon carcinoma line, DLD-1, did not express TIMP-3. If down regulation of TIMP-3 is causally related to carcinogenesis, re-expression by transfection may reverse the tumor cell phenotype. We therefore overexpressed human TIMP-3 in DLD-1 cells. TIMP-3 transfectants showed a serum-dependent growth inhibition in monolayer culture and a decreased growth potential in nude mice in a manner dependent on the level of TIMP-3 expression. A transfectant expressing a high level of active hTIMP-3 completely lost the ability to form tumors following s.c. injection into nude mice. We also tested TIMP-3 expressing cells and neocontrol TIMP-3 negative cells for their ability to grow in liquid suspension culture, since both cells grew in semi-solid soft agar. As compared to neocontrol cells, TIMP-3 overexpressors formed large aggregates, followed by cell death. This effect was not mimicked by BB94, a broad MMP inhibitor. We conclude from this study that (i) TIMP-3 overexpression in human colon carcinoma cells induces growth arrest in low serum conditions and inhibits in vivo tumor growth and (ii) the TIMP-3-induced large aggregate formation and subsequent cell death under suspension growth cannot be explained by its MMP inhibitory activity.

Animals↗
PubMed1996

Mortality of passerines adjacent to a North Carolina corn field treated with granular carbofuran.

Red-winged blackbirds (Agelaius phoeniceus) were collected during an epizootic in southeastern North Carolina (USA). Activity of brain cholinesterase (ChE) was inhibited by 14 to 48% in three of five specimens, and returned to normal levels after incubation. Gastrointestinal tracts were analyzed for 30 anti-ChE agents. Carbofuran, the only compound detected, was present in all specimens at levels from 5.44 to 72.7 micrograms/g wet weight. Application of granular carbofuran in an adjacent corn field, results of necropsy examinations, and chemical analyses are consistent with a diagnosis of carbofuran poisoning in these specimens.

Animals↗
PubMed1995

Polo-like kinase is a cell cycle-regulated kinase activated during mitosis.

Previously, we demonstrated that expression of polo-like kinase (PLK) is required for cellular DNA synthesis and that overexpression of PLK is sufficient to induce DNA synthesis. We now report that the endogenous levels of PLK, its phosphorylation status, and protein kinase activity are tightly regulated during cell cycle progression. PLK protein is low in G1, accumulates during S and G2M, and is rapidly reduced after mitosis. During mitosis, PLK is phosphorylated on serine, and its serine threonine kinase function is activated at a time close to that of p34cdc2. The phosphorylated form of PLK migrates with reduced mobility on SDS-polyacrylamide gel electrophoresis, and dephosphorylation by purified protein phosphatase 2A converts it to the more rapidly migrating form and reduces the total amount of PLK kinase activity. Purified p34cdc2-cyclin B complex can phosphorylate PLK protein in vitro but causes little increase in PLK kinase activity.

Amino Acid Sequence↗
PubMed1995

Metabolic characterization of human non-Hodgkin's lymphomas in vivo with the use of proton-decoupled phosphorus magnetic resonance spectroscopy.

Development of biological and clinical uses of in vivo 31P magnetic resonance spectroscopy has been hampered by poor anatomic localization of spectra and poor resolution of overlapping signals within phosphomonoester and phosphodiester regions of the spectrum. We applied 1H-decoupling and nuclear Overhauser enhancement to improve resolution of 31P magnetic resonance spectra accurately localized to 21 non-Hodgkin's lymphomas (NHL) by using three-dimensional chemical shift imaging. All 21 spectra had large phosphomonoester signals (26% of total phosphorus) that contained high amounts of phosphoethanolamine relative to phosphocholine. There were no signals from glycerophosphoethanolamine or glycerophosphocholine but only a broad signal from membrane phospholipids in the phosphodiester region (20% of phosphorus). Prominent nucleoside triphosphates (47% of phosphorus) and low inorganic phosphate (7% of phosphorus) indicate well-perfused tissue with viable cells. Mean intracellular pH was 7.23. These characteristics were similar in all grades and stages of NHL. By analogy with recently reported studies in cell lines in vitro, we hypothesize that the pattern of phospholipid metabolites observed in NHL in vivo is partly a manifestation of sustained activation of phospholipase C or D. The techniques we implemented permitted us to obtain more information about in vivo metabolism of NHL than has heretofore been available. This information is important for the establishment of appropriate experimental models and provides a basis from which to examine potential clinical uses of 31P magnetic resonance spectroscopy.

2,3-Diphosphoglycerate↗
PubMed1995

Prostate-specific antigen messenger RNA is expressed in non-prostate cells: implications for detection of micrometastases.

Prostate specific antigen (PSA) is generally believed to be expressed only by prostate epithelium. If this were true of PSA, RNA, then detecting PSA RNA in cells outside of the prostate would indicate metastasis. PCR can detect rare prostate cancer cells. To enhance sensitivity, we developed "nested primer" PCR to detect PSA RNA. With this method, PSA RNA is present in several non-prostate cell lines, including BG-1 (ovarian), SK-MES-1 (lung), and HL-60 (myeloid leukemia), and some normal blood. A low level of PSA RNA detectable by nested primer PCR is present in some cells of non-prostate origin and may interfere with sensitive methods to detect micrometastases. Transcripts of other genes thought to be organ specific may have similar limitations.

Adenocarcinoma↗
PubMed1995

Heterogeneity of the aggregation response of human platelets to arginine vasopressin.

Previous reports have alluded to variability in the aggregation response of normal human platelets to the neuropeptide arginine vasopressin (AVP). Since it has not been well documented, the current studies were undertaken to characterize this response. AVP (1-100 nM) produced a concentration-dependent aggregation response. Although the aggregation response to 100 nM AVP did not correlate with age or sex, there was a bimodal response distribution based on the presence or absence of a second wave of aggregation. In kinetic studies, the apparent km of AVP was 18.3 +/- 5.4 nM. There was a significant inverse relationship between the maximal aggregation response to 100 nM AVP and the km (r = -0.82). One hundred nanomolar AVP increased the intracellular calcium concentration of platelets by 406 +/- 120 nM in calcium free buffer and by 658 +/- 233 nM in the presence of 1.0 mM CaCl2. The aggregation response to 100 nM AVP correlated most strongly with the transmembrane influx of calcium (r = 0.84). In individuals whom 100 nM AVP was able to generate a second wave of aggregation, the selective protein kinase C inhibitor bis-indolylmaleimide significantly decreased the platelet aggregation response. Thus, there is significant heterogeneity in the aggregation response of normal human platelets to AVP. Based on our kinetic studies and the effects of PKC inhibition on the aggregation response to AVP, we would hypothesize that the variability of the aggregation response of normal human platelets to AVP is related to a polymorphism of the platelet AVP V1 receptor.

Age Factors↗
PubMed1995

Haloperidol blocks the uptake of [18F]N-methylspiroperidol by extrastriatal dopamine receptors in schizophrenic patients.

We had previously demonstrated extrastriatal uptake of [18F]N-methylspiroperidol (18F-NMS) in the human brain. This study evaluates the effect of haloperidol on 18F-NMS binding in extrastriatal brain regions. Six schizophrenic patients on haloperidol underwent two PET scans with 18F-NMS at 12 h and at 6 days after haloperidol withdrawal. There was a significant increase in 18F-NMS uptake in striatal, thalamic, and temporal regions but not in frontal, occipital, or cerebellar regions, following drug withdrawal. Haloperidol's ability to block the uptake of 18F-NMS is an indication of the specificity of the radioligand's binding in these regions and supports the postmortem data demonstrating the presence of dopamine D2 receptors in the thalamus and temporal cortex of the human brain.

Adult↗
PubMed1995

Treatment-related myelodysplastic syndrome following abdominopelvic radiotherapy for endometrial cancer.

A patient with grade II endometrial adenocarcinoma underwent TAH/BSO. The tumor penetrated 50% of the myometrium. A lesion from the serosa of the sigmoid colon was removed and contained metastatic adenocarcinoma. Metastatic tumor was also found in the common iliac lymph nodes. Postoperatively the patient was treated with abdominopelvic radiotherapy to 30 Gy. The pelvis was boosted to a dose of 46.2 Gy. The vaginal apex was then treated with three applications of high-dose-rate brachytherapy to a total dose of 12 Gy. The patient was doing well with no evidence of recurrence 52 months following treatment when she was diagnosed with a myelodysplastic syndrome. Cytogenetic analysis revealed aberrations of chromosomes 5 and 7, which is highly suggestive of a treatment-related process. Myelodysplasia induced by radiotherapy alone is an unusual but recognized event.

Abdomen↗
PubMed1995

Pulsatile pelvic masses: options for evaluation and management of pelvic arteriovenous malformations.

Three recent and previously unreported cases of pelvic arteriovenous malformation are presented. Two were surgically resected in conjunction with elective gynecologic surgery, and the third was embolized by retrograde femoral superselective coaxial catheterization. The causal significance of birth or surgical trauma is discussed, and guidelines for diagnostic angiographic imaging and therapeutic embolization are presented.

Adult↗
PubMed1995

Insoluble Glucan Formation by Leuconostoc mesenteroides B-1355.

Leuconostoc mesenteroides B-1355 produced at least three glucosyltransferases (GTFs). We previously identified GTF-2 as alternansucrase and GTF-3 as fraction L dextransucrase. We here show that GTF-1 is a previously unreported sucrase that synthesized water-insoluble dextran. Our evidence consisted of the following. (i) GTF-1 was a major component and GTF-2 was a minor component of culture supernatant fractions, but supernatant fractions actively synthesized water-insoluble glucan. (ii) GTF-1 and culture supernatants produced an unusual high-pressure liquid chromatography pattern of malto-oligosaccharides that was not reproduced by GTF-2-GTF-3 mixtures. (iii) GTF-2, GTF-3, and GTF-2-GTF-3 mixtures did not synthesize insoluble glucan from sucrose. Nearly all of the alternansucrase in young (less than 17-h) cultures was associated with the cells.

Journal Article↗
PubMed1995

Prothymosin alpha: in search of a function.

Prothymosin alpha is an acidic nuclear protein that is expressed at high levels in a wide variety of cell types. Accumulating data correlate prothymosin expression with alterations in the proliferative state of cells. Some data indicates that prothymosin may actually be necessary, if not sufficient, for proliferation, and that prothymosin may function in a c-myc associated pathway. Prothymosin is highly conserved through evolution suggesting a key function, however, that function remains unknown.

Animals↗
PubMed1995

Application of brain cholinesterase reactivation to differentiate between organophosphorus and carbamate pesticide exposure in wild birds.

Brain cholinesterase activity was measured to evaluate pesticide exposure in wild birds. Thermal reactivation of brain cholinesterase was used to differentiate between carbamate and organophosphorus pesticide exposure. Brain cholinesterase activity was compared with gas chromatography and mass spectrometry of stomach contents. Pesticides were identified and confirmed in 86 of 102 incidents of mortality from 29 states within the USA from 1986 through 1991. Thermal reactivation of cholinesterase activity was used to correctly predict carbamates in 22 incidents and organophosphates in 59 incidents. Agreement (P < 0.001) between predictions based on cholinesterase activities and GC/MS results was significant.

Animals↗