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Biomedical subjects

M L O'Connor

Publications and source records attributed to M L O'Connor.

At least 19 recordsLinked to original sources

Immunoglobulin D benign monoclonal gammopathy. A case report.

The authors report a case, perhaps the first, of immunoglobulin D (IgD) benign monoclonal gammopathy. The patient, a 48-year-old black woman, initially had a 500 mg/dl IgD-lambda M-spike, hypercalcemia, and anemia. There was no bone pain, lytic bone lesions, or evidence of renal failure. The bone marrow showed 2.8% plasma cells with a diffuse (not nodular) IgD plasmacytosis and strong lambda predominance. Only trace amounts of free lambda light chains could be demonstrated by immunoelectrophoresis in serum and concentrated urine. The anemia responded quickly to iron therapy. Chemotherapy was not initiated. Over the 6+ years of follow-up, the patient has had no progression of clinical disease attributable to her IgD monoclonal gammopathy. The IgD M-spike has steadily decreased.

Blood Protein Electrophoresis

Bone marrow and peripheral blood findings in patients with extreme thrombocytosis. A report of 63 cases.

Sixty-three bone marrow (BM) and peripheral blood specimens from patients with platelet counts of 1000 x 10(9)/L or greater were examined in an attempt to determine if any BM or peripheral blood findings could be used reliably to distinguish primary thrombocythemia from other myeloproliferative disorders and extreme examples of reactive thrombocytosis. Our results indicated that the BM findings in primary thrombocythemia were quite similar to those in polycythemia vera and chronic granulocytic leukemia with associated extreme thrombocytosis. However, statistically significant differences between the BM findings in myeloproliferative disorders and extreme reactive thrombocytosis were found in the numbers of megakaryocytes, presence or absence of megakaryocyte clusters, stainable iron, cellularity, and reticulin content. We concluded that BM examination is a useful procedure as an aid in determining the cause of extreme thrombocytosis.

Bone Marrow

Albuminuria vs urinary total protein for detecting chronic renal disorders.

A literature review and our own data are presented to demonstrate that urinary albumin (UA) excretion increases in many renal disorders and that it offers a far more sensitive indicator than the commonly used urinary total protein (UTP) for the early detection of renal involvement in many chronic diseases such as diabetes mellitus, hypertension, and systemic lupus erythematosus. In many individuals with these disorders, UA increases severalfold, even while UTP remains within the reference interval. UA is also more suited than UTP for following therapeutic responses in these slowly progressive renal disorders. Increases in UA are associated with increased mortality. UTP measurements are plagued with many analytical problems, whereas UA is much easier to standardize. We recommend that both UA and UTP be measured when quantitative urine protein assays are ordered, especially when the UTP is less than 300 mg/g of creatinine.

Albuminuria

Altered regulation of platelet-derived growth factor A-chain and c-fos gene expression in senescent progeria fibroblasts.

The study of human genetic disorders known as premature aging syndromes may provide insight into the mechanisms of cellular senescence. These diseases are clinically characterized by the premature onset and accelerated progression of numerous features normally associated with human aging. Previous studies have indicated that fibroblasts derived from premature aging syndrome patients have in vitro growth properties similar to senescent fibroblasts from normal individuals. As an initial approach to determine whether gene expression is altered in premature aging syndrome fibroblasts, RNA was prepared from various cell strains and used for gel blot hybridization experiments. Although normal fibroblasts only express platelet-derived growth factor (PDGF) A-chain mRNA for a brief period following mitogenic stimulation, one strain of Hutchinson-Gilford (progeria) syndrome fibroblasts, AG3513, constitutively expresses PDGF A-chain mRNA and PDGF-AA homodimers. The PDGF A-chain gene does not appear to be amplified or rearranged in these fibroblasts. AG3513 progeria fibroblasts have properties characteristic of senescent cells, including an altered morphology and a diminished mitogenic response to growth promoters. The diminished response of AG3513 progeria fibroblasts to PDGF stimulation was examined in some detail. Studies using 125I-PDGF-BB, which binds with high affinity to both A- and B-type PDGF receptors, indicate that normal and AG3513 progeria fibroblasts have a similar number of PDGF receptors. Although receptor autophosphorylation occurs normally in PDGF-stimulated AG3513 progeria fibroblasts, c-fos mRNA induction does not. The senescent phenotype of AG3513 fibroblasts is probably unrelated to their constitutive PDGF A-chain gene expression; further studies are necessary in order to directly address this issue. Also, additional analysis of this progeria fibroblast strain may provide information on the control of mitogen-inducible gene expression in normal cells.

Adolescent

The diagnosis of microcytic anemia by a rule-based expert system using VP-Expert.

We describe our experience in creating a rule-based expert system for the interpretation of microcytic anemia using the expert system development tool, VP-Expert, running on an IBM personal computer. VP-Expert processes data (complete blood cell count results, age, and sex) according to a set of user-written logic rules (our program) to reach conclusions as to the following causes of microcytic anemia: alpha- and beta-thalassemia trait, iron deficiency, and anemia of chronic disease. Our expert system was tested using previously interpreted complete blood cell count data. In most instances, there was good agreement between the expert system and its pathologist-author, but many discrepancies were found in the interpretation of anemia of chronic disease. We conclude that VP-Expert has a useful level of power and flexibility, yet is simple enough that individuals with modest programming experience can create their own expert systems. Limitations of such expert systems are discussed.

Anemia

Antibody-nucleic acid interactions. Antibodies to psoralen-modified RNA as probes of RNA structure.

Antisera elicited by immunization of rabbits with 4'-aminomethyl-trioxsalen (AMT)-modified poly(A,U) complexed with methylated bovine serum albumin was characterized in competition radioimmunoassays (RIA) and enzyme-linked immunosorbent assays (ELISA). AMT-poly(A,U) was over 10,000-fold more reactive than unmodified poly(A,U) or AMT alone. The antiserum cross-reacted to varying extents with AMT-modified-RNA's and -DNA's. The presence of AMT-uridine usually assured strong reactivity. The amino group of AMT contributed to antibody binding to a small degree. Binding was not significantly affected by high ionic strength, suggesting that binding does not involve ion pair formation. Murine encephalomyocarditis virus replicative intermediates, as well as cellular RNA and DNA were modified by psoralen in intact cells, suggesting that EMCV RNA and cellular RNA's in intact cells possess detectable stretches of base pairs. The antibodies described here will be useful in studying the secondary and tertiary structure of RNA's in vitro and in intact cells.

Animals

Red blood cell antibody identification and confirmation using commercial panels. A computer program for the IBM personal computer.

A menu-driven computer program that utilizes a data base of commercial panels was developed to assist in the identification and confirmation of red blood cell antibodies. A selected panel, along with the corresponding serum reactions, is displayed on the monitor and possible antibody patterns including dosage-dependent patterns are highlighted. A panel interpretation is then printed that includes a list of the possible (nonexcluded) antibodies, a probability level of identification for each possible antibody, and a table of antibody characteristics to aid in the differentiation among the possible antibodies. The panel data base can also be searched for additional red blood cells of specified phenotypes to confirm each suspected antibody. These additional red blood cells may be combined into a temporary panel for computer analysis. The program can also enter, print, edit, and delete any commercial panel from the data base. This computer program has proved to be faster and more accurate than the standard manual method for panel analysis, especially when multiple antibodies are present.

Antibodies

A comparison of antibiotic susceptibility profiles using single and multiple isolates per patient.

We compared the antibiogram statistics generated by including all clinical isolates to those obtained by tabulating no more than one isolate of a particular organism from a given patient. We found that 48.3% of the isolates presented multiple occurrences in individual patients but found no practical differences in the profiles obtained by the two methods. We also tabulated the occurrence of minimum inhibitory concentration (MIC)-distinct organisms among the sets of multiple isolates of E. coli and of S. aureus and found that only 20.9% of those isolates represented duplicate organisms by MIC profile. This heterogeneity of MIC sensitivity that occurs in multiple isolates from individual patients was not expected but provides an explanation for the lack of difference between the two methods of tabulating antibiotic susceptibility statistics.

Bacterial Infections

Rapid identification of Clostridium species by high-pressure liquid chromatography.

High-pressure liquid chromatography was evaluated as a rapid means of identifying various species of clostridia. Isolates were inoculated into a defined medium and incubated aerobically for 1 h at 35 degrees C. The organisms were removed, and the supernatants were derivatized for 1 min at room temperature by the addition of o-phthalaldehyde. The total time required to run each chromatogram was approximately 50 min. Standardized peak heights for each medium component and any new peaks formed were calculated for each isolate and compared with those for uninoculated control medium. Multiple isolates of various Clostridium species gave consistent patterns of medium utilization that could be used for identification. This rapid method can easily be adapted for laboratory use and has the potential for automation.

Amino Acids

Effect of adrenocorticotropic hormone and associated hormonal responses on semen quality and sperm output of bulls.

The objective was to determine if semen quality and output could be affected by pharmacological doses of adrenocorticotropin. Three Holstein bulls, one 7 yr old and two yearlings, were treated with 200 IU adrenocorticotropic hormone every 8 h for 6 days. Effects of treatment on semen traits and peripheral concentrations of glucocorticoids, testosterone, and androstenedione were measured. Viability of spermatozoa (percentage motility and percentage intact acrosomes), ejaculate volume, sperm concentration, and weekly sperm output were unaffected by adrenocorticotropin treatment up to 8 wk posttreatment. The proportion of spermatozoa with cytoplasmic droplets and head abnormalities was elevated slightly from .8 +/- .1 and 4.2 +/- .3% to 1.3 +/- .2 and 5.8 +/- .4% during treatment. Total glucocorticoids increased from 11.9 +/- 2.7 ng/ml before treatment to 73.5 +/- 4.1 ng/ml during treatment. Testosterone decreased in the yearling bulls from 5.5 +/- .9 ng/ml plasma before treatment to .5 +/- .5 ng/ml afterward; the decrease began 8 h following the initial adrenocorticotropin injection and persisted until 24 h following last injection. The mature bull had normal testosterone concentrations for the first 4 days of injection, and decreased concentrations for the last 2 days of injection. Semen viability, concentration, and sperm output are unaffected by a pharmocological administration of adrenocorticotropin and subsequent marked increase of glucocorticoids and decrease of testosterone. Only a small increase of semen content of immature sperm or sperm with abnormal heads may be associated with these marked endocrine changes.

Adrenocorticotropic Hormone

Hepatitis-B: a review.

The recent literature on various aspects of hepatitis-B is reviewed with emphasis on the interrelationships of viral structure, antigenic components, and host immune response in acute, chronic, and asymptomatic carrier states of the infection. The mode of replication and mechanisms of transmission are discussed. Special attention is paid to potential non-parenteral routes of spread. The role of hepatitis-B in associated immune complex diseases and in hepatoma is outlined. A guide to the interpretation of serologic tests for hepatitis-B associated antigen and antibody patterns is presented in relation to the clinical stage and prognosis of the infection. Therapy, except in conceptual terms, is not covered but a summary of the current status of active and passive immunization is given. The unresolved question of the infectivity of carrier medical staff for their patient contacts, and the reverse, is discussed.

Acute Disease