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F W Miller

Publications and source records attributed to F W Miller.

88 records · Page 5Linked to original sources
PubMed1987

Prevalence of thyroid disease and abnormal thyroid function test results in patients with systemic lupus erythematosus.

Although thyroid disease has been associated with other autoimmune conditions, it is not well recognized in systemic lupus erythematosus (SLE) patients. We found that in 332 SLE patients hospitalized during a 5-year period, the overall prevalence of diagnosed thyroid disease (7.5%) was similar to that in other female populations, but the prevalence of diagnosed hypothyroidism (6.6%) was unexpectedly high. There was also a high frequency of abnormal thyroid function test results in 175 SLE patients without diagnosed thyroid disease who underwent laboratory screening. More than 45% of these patients had elevated levels of thyroid-stimulating hormone, 34% had low T3 determinations, and 18% had high antimicrosomal antibody titers. When patients were categorized into "functional groups," some showed evidence of the "euthyroid sick syndrome" (15%), but many more had laboratory test results suggestive of true (5%) or incipient (39%) primary hypothyroidism. We conclude that abnormal thyroid function test results are common in patients with SLE and that hypothyroidism, especially, should be considered when evaluating symptoms and signs in SLE patients.

Adolescent↗
PubMed1984

Evidence for major differences in ribosomal subunit proteins from Plasmodium berghei and rat liver.

Purified polysomes were isolated in high yield from the erythrocytic stages of the rodent malaria parasite, Plasmodium berghei, and from rat liver. Proteins extracted from the ribosomal subunits derived from these polysomes were fractionated and their number and molecular weights were estimated by two-dimensional polyacrylamide gel electrophoresis. Plasmodial small ribosomal subunits contained 30 proteins ranging in apparent molecular size from 11.7 to 40.7 kDa, while large subunits contained 35-36 proteins ranging from 12.1 to 42.6 kDa. None of these parasite proteins was shared by the two subunits nor altered in electrophoretic mobility by radioiodination. Rat liver 40 S ribosomal subunit proteins numbered 30 and ranged from 9.2 to 37.5 kDa, while liver 60 S subunits contained 41-43 proteins with apparent molecular sizes of 10.3-45.2 kDa. Coelectrophoresis of trace amounts of radioiodinated P. berghei ribosomal subunit proteins and stainable quantities of liver proteins demonstrated that most of these 139 parasite and host ribosomal proteins possessed different two-dimensional electrophoretic mobilities under the conditions of this study. Based upon a comparative analysis of P. berghei and rodent ribosomal RNA and these data, it was concluded that parasite and host ribosomes contain distinct ribosomal RNAs and ribosomal proteins.

Animals↗
PubMed1984

Urinary cancer-related protein EDC1 and serum inter-alpha trypsin inhibitor in breast cancer.

In 1976 we isolated a novel glycoprotein labeled EDC1, Mr 27,500, which is immunologically related to the normal plasma protein inter-alpha trypsin inhibitor (IATI, Mr 160,000) and which is the major component of cancer-associated proteinuria. Urinary excretion of EDC1 (mg/g creatinine) may be classified in four ranges: i) low (less than 15); ii) light (15-30); iii) intermediate (31-45); and iv) heavy (greater than 45). Normal healthy women excrete 8.0 +/- 2.2 mg/g creatinine (average +/- SEM), whereas patients with metastatic breast cancer excrete 98.2 +/- 11.6 mg/g creatinine. Patients with a variety of non-malignant disorders excreted 14.6 +/- 4 mg EDC1/g creatinine, but patients with renal failure, rheumatoid arthritis, and infectious diseases averaged 130.3 +/- 60. Sixty-five to 95 percent of urinary immunoreactive EDC1 in the latter group was of higher molecular weight, perhaps reflecting increased renal clearance of plasma IATI. In patients undergoing excisional biopsy of breast lesions, preoperative EDC1 excretion was 21.5 +/- 3.4 in those whose lesions were benign and 43.1 +/- 7.6 in those whose lesions were malignant. Eight of these latter patients were heavy excretors; EDC1 excretion fell postoperatively in these patients. In normal serum the immunoreactive IATI (IR-IATI) exists in three molecular weight forms 160,000, 120,000 and 58,000. In patients who were heavy excretors of EDC1, the IR-IATI corresponding to Mr 58,000 was absent and total serum IR-IATI was about two-thirds of normal. There was also a negative correlation between serum levels of IATI and urinary EDC1 in these patients. These data suggest that urinary EDC1 may arise as a result of interaction between IATI and tumor-associated proteases.

Alpha-Globulins↗
PubMed1984

Abnormal profile of serum proteinase inhibitors in cancer patients.

We reported previously that an antitryptic glycoprotein, EDC1 (Mr 27,500), which is immunologically related to the normal serum proteinase inhibitor, inter-alpha-trypsin inhibitor (IATI), is excreted in large quantities in the urine of metastatic cancer patients. We have now measured immunoreactive titers of urinary EDC1 and five serum proteinase inhibitors (including IATI) in 16 patients with hematological cancers, 9 patients with various solid tumors, and 32 healthy subjects. The mean urinary EDC1 levels were 22-fold greater in all cancer patients as compared to normals [187.0 +/- 136.6 (S.D.) versus 8.4 +/- 8.2 mg/g creatinine; p less than 0.001]. In the cancer group, serum levels of immunoreactive alpha 1-proteinase inhibitor (also called alpha 1-antitrypsin), alpha 1-antichymotrypsin, and C1 inactivator averaged 152, 237, and 165% of the normal values, respectively (p less than 0.01). Immunoreactive alpha 2-macroglobulin levels were unchanged, and immunoreactive IATI levels were depressed (75% of the normals; p less than 0.01). The lower levels of IATI and elevated levels of EDC1 are consistent with the latter being derived from the former. In spite of the increased immunoreactive alpha 1-proteinase inhibitor level, the serum antitryptic capacity of the cancer group averaged only 50% of the normal group (p less than 0.01; range, 5 to 110% of normal average). This suggests that about 70% of the serum alpha 1-proteinase inhibitor in the cancer group is functionally inert.

Adolescent↗
PubMed1978

The ribosomes of Plasmodium berghei: isolation and ribosomal ribonucleic acid analysis.

Ribosomes and high molecular weight ribosomal ribonucleic acid (rRNA) from the blood stages of Plasmodium berghei parasites were studied in preparations free from host ribosome contamination. Purified malarial ribosomes were isolated in high yield from a population of ultrastructurally intact, viable parasites by hypertonic lysis with Triton X-100 and differential centrifugation. These ribosomes were shown to be derived from active polysomes and could be dissociated into subunits by puromycin-0.5 M KCl treatment. Malarial rRNA extracted from purified 40S and 60S ribosomal subunits was characterized by electrophoretic, sedimentation and base ratio analyses. Like certain other protozoa, the P. berghei 40S ribosomal subunit possessed an exceptionally large RNA species (mol. wt 0.9 X 10(6), while RNA isolated from the parasite's 60S subunit (mol. wt 1.5 X 10(6)) was specifically 'nicked' to produce one large component (mol.wt 1.2 X 10(6)) and one small component (mol.wt 0.3 X 10(6)) in equimolar quantities. These rRNA's migrate identically on polyacrylamide gels after heating to 63 degrees C for 5 min or under denaturing conditions in the presence of formamide, indicating an absence of aggregation and non-specific degradation of the rRNA species. Base composition studies showed P. berghei rRNA to be low in guanosine and cytosine content, as is the case for protozoa generally.

Animals↗
PubMed1977

Influence of 9-beta-D-arabinofuranosyladenine on total protein synthesis and on differential gene expression of unique proteins in the rodent malarial parasite Plasmodium berghei.

The antibiotic 9-beta-D-arabinofuranosyladenine is a drug with a broad spectrum of activity against animal viruses, with little or no effect on mammalian cells, when administered in vivo or in vitro. Here we report that the antibiotic markedly inhibited the incorporation of [35S]methionine into malarial protein. Inhibition was apparent when the parasites were either exposed to the drug in vivo during the course of infection or incubated with the drug in vitro. Moreover, the antibiotic induced pronounced changes in the spectrum of proteins synthesized. Some proteins that are prominently apparent in the control disappear from the drug-treated parasites; others specific for drug-treated parasites appear, indicating changes in the commitment for gene expression as manifested by the appearance of the final protein product. Proteins synthesized were analyzed by two-dimensional polyacrylamide gels; the first dimension used isoelectric focusing in cylinder gels and the second dimension used electrophoresis in a lithium dodecyl sulfate slab gel. Proteins were visualized by radioautography.

Animals↗
PubMedDate not supplied

Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies. Childhood Myositis Heterogeneity Collaborative Group.

We identified maternal microchimerism by fluorescence in-situ hybridisation in magnetically-separated CD4 or CD8 peripheral blood cells of eight of nine male patients with juvenile idiopathic inflammatory myopathy, compared with two of nine healthy male controls. We also found maternal microchimerism in inflammatory lesions (one skin sample and nine muscle biopsy samples) of all ten patients examined, compared with two of ten biopsy samples from patients with other muscle disorders. These results suggest that maternal cells may be involved in the pathogenesis of juvenile idiopathic inflammatory myopathy.

Adolescent↗
PubMedDate not supplied

Molecular detection of persistent Borrelia burgdorferi in a man with dermatomyositis.

A 40-year-old white man with a several year history of various immunologic disorders, including anti-Jo-1 autoantibody positive dermatomyositis, developed clinical Lyme disease after being biten by a tick. The patient was treated with oral tetracycline and his initial symptoms resolved; however, he suffered an exacerbation of his muscle disease which was difficult to control despite cytotoxic therapy. Antibiotic therapy was reinstituted after Borrelia burgdorferi was detected in the patient's peripheral blood leukocytes by the polymerase chain reaction (PCR). All serologic, T-cell stimulation, and western blot analyses, however, were negative. The patient's disease responded to oral ampicillin, probenecid therapy and concurrent cytotoxic therapy. Subsequent leukocyte PCR testing has been negative for the causative agent of Lyme disease. This case may provide an example of the in vivo immuno-modulatory effects of spirochetes in human autoimmune disease. In addition, this case emphasizes the potential clinical utility of PCR technology in evaluating the persistent sero-negative Lyme disease which may occur in immunocompromised individuals.

Administration, Oral↗
PubMedDate not supplied

Abnormalities of the immune system in the idiopathic inflammatory myopathies.

This brief report reviews some of the major studies presenting evidence for altered humoral and cellular immunity in the idiopathic inflammatory myopathies. Clearly, the association of these disorders with other autoimmune diseases, the myriad of myositis-associated autoantibodies, and the phenotypic and functional abnormalities of mononuclear cells from PM/DM patients, all suggest that autoimmune mechanisms are central and pervasive aspects of these diseases. Yet, the current experimental limitations in immunology, as well as the rarity and heterogeneity of the idiopathic inflammatory myopathies, combine to limit our understanding of which factors are primary, and which are only secondary epiphenomena, in the complex pathogenesis of these disorders.

Antibody Formation↗