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Biomedical subjects

K L Miller

Publications and source records attributed to K L Miller.

At least 19 recordsLinked to original sources

Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation.

A 25-kDa homodimeric protein was purified from demineralized bovine bone extract and identified as activin A. The bovine bone activin enhanced formation of ectopic bone in rat subcutis when implanted in combination with partially purified bovine bone morphogenetic protein (BMP-2, BMP-3) in collagen/ceramic carrier. The implants, removed at 14 days, contained markedly elevated levels of alkaline phosphatase activity. Histological examination revealed an extensive formation of woven bone with very little cartilage. In contrast, a combination of transforming growth factor-beta 2 and BMP promoted formation of bone with an abundance of cartilage. The implants with BMP alone exhibited some osteoinductive activity, while the implants with activin alone showed no activity. These results demonstrate that bone is a rich source of activin and that activin plays an important role in modulating bone formation.

Activins

Quality assurance and reproducibility of high-resolution two-dimensional electrophoresis and silver staining in polyacrylamide gels.

Qualitative data from high-resolution two-dimensional electrophoresis (2DE) have become clinically useful in immunoglobulin clonality analysis, in resolution of ambiguities in immunofixation typing of paraproteins, and in genetic typing of serum proteins. Since 1986, the authors have been evaluating the College of American Pathologists Reference Preparation for Serum Proteins (RPSP) as a quality control material for 2DE because (1) it is prepared exclusively from pooled human sera, (2) the pool yields a reference pattern of mixed heterozygosity for genetic markers, and (3) RPSP is widely available as a lyophilized preparation that currently serves in the authors' laboratory as a qualitative quality control preparation and that may become a quantitative quality control material or external quality assessment material for 2DE. Using the ISO-DALT 2DE system and silver-staining, the peptide patterns were examined in 11 lots of RPSP and compared with fresh serum and with each other. Consistent differences in the 2DE pattern between RPSP and fresh serum included the presence of freeze-thaw peptides, the presence of degradation spots of apolipoprotein A-I, and the diminution of apolipoprotein spot intensities in RPSP. All lots of RPSP yielded clear identification of the eight serum proteins used for quality control calculations. Run-to-run coefficients of variation for a single lot of RPSP for four parameters of 2DE spot location and gradient reproducibility were comparable with band location reproducibility for the one-dimensional procedures of serum protein electrophoresis and lactate dehydrogenase isoenzyme electrophoresis. It is concluded that the reproducibility, that is, imprecision, of 2DE is the same as one-dimensional clinical electrophoresis techniques and that either RPSP or pooled fresh serum can serve as a satisfactory internal quality control material.

Blood Protein Electrophoresis

Alternatives to estrogen for menopausal symptoms.

It is not within the scope of this chapter to discuss the long-term effects of menopause, such as osteoporosis or heart disease, or to disentangle the complex psychosocial complications and treatments of menopausal mood disorders. All long-term consequences of hypoestrogenism are more amenable to prevention than to cure, as are all the negative consequences of aging. Women should maintain regular physical activity, consume a diet low in fat and high in fiber, ensure adequate calcium intake, and possibly lower animal protein consumption. Moreover, they should know their cholesterol levels and undergo regular physical examinations with an emphasis on health maintenance. Despite the many advantages of estrogen replacement therapy, it is not appropriate for all women. Cultural, personal, and medical considerations may eliminate the use of estrogen, in which case it is important to offer alternative medical advice and direction to minimize bothersome symptoms of menopause and enhance the quality of life.

Adult

Obstructing endobronchial bands complicating radiation therapy for lung carcinoma.

A 57-year-old man with small cell lung carcinoma developed benign, obstructing endobronchial bands five months after external beam radiation therapy. We believe that this represents an unusual delayed complication of radiation therapy for airway tumors. An excellent clinical response was obtained after laser ablation of the lesion.

Antineoplastic Combined Chemotherapy Protocols

Alterations in erythropoiesis in TGF-beta 1-treated mice.

Chronic treatment of mice with transforming growth factor beta 1 (TGF-beta 1) resulted in a dose-dependent inhibition of erythropoiesis. Following 14 daily s.c. injections of 5 or 25 micrograms of TGF-beta 1, a significant degree of anemia was observed. In addition, erythroid progenitor cells were present in reduced numbers in the bone marrow and spleen. Pluripotent stem cells were present in normal numbers in the bone marrow of mice treated with 25 micrograms of TGF-beta 1. However, significantly elevated levels were present in the peripheral blood. Adequate levels of erythropoietin were present in TGF-beta 1-treated mice. Following suspension of treatment with TGF-beta 1, erythropoiesis was restored, and TGF-beta-treated mice were able to compensate the anemia. One week following treatment, only mice treated with 25 micrograms of TGF-beta 1 continued to show evidence of anemia. However, in contrast to 1 day following treatment, these mice had levels of reticulocytes that were significantly above control values. In addition, erythroid progenitor cells had returned to normal levels in the bone marrow and were present in elevated levels in the spleen in both groups of TGF-beta 1 treated mice. The results provide evidence that the anemia associated with sustained TGF-beta 1 treatment is the result, in part, of a reversible inhibition of the maturation of erythroid progenitor cells.

Anemia

Diagnostic radiology peer review: a method inclusive of all interpreters of radiographic examinations regardless of specialty.

A proposed method of assessing the quality of diagnostic radiographic examinations includes peer review designed to evaluate physicians, including nonradiologists, involved in the performance and interpretation of such examinations. A pilot project evaluated this system with randomly selected Pennsylvania Blue Shield data files of 10 providers billing for chest radiography interpretations during the second quarter of 1989. Of the 98 chest radiographs reviewed blindly, all inadequately marked radiographs and incomplete written reports were produced by nonradiologists. Technical quality of images obtained by radiologists did not significantly differ from that of images obtained by nonradiologists (P = .189). All five interpretive errors that could have seriously affected the patient's health care were produced by nonradiologists (P = .019). Four of these serious errors were made by providers billing for fewer than 25 radiographs. While administrative and time cost limitations are obvious, this method of peer review encompasses all physicians billing for a particular radiographic service, irrespective of specialty.

Blue Cross Blue Shield Insurance Plans

Lowe oculocerebrorenal syndrome in a female with a balanced X;20 translocation: mapping of the X chromosome breakpoint.

A Hispanic girl with Lowe oculocerebrorenal syndrome (OCRL), an X-linked recessive condition characterized by cataracts, glaucoma, mental retardation, and proteinuria, is reported. A balanced X;20 chromosomal translocation with the X chromosome breakpoint at q26.1 was found with high-resolution trypsin-Giemsa banding. Somatic cell hybridization was used to separate the X chromosome derivative and the chromosome 20 derivative in order to position, with respect to the translocation breakpoint, several DNA loci that are linked to the Lowe syndrome locus (Xq24-q26). DXS10 and DXS53 were found to be distal to the breakpoint, whereas DXS37 and DXS42 were located proximal to it. These studies suggest that the OCRL locus lies in the region between these probes. The translocation chromosome originated from an unaffected male without a visible translocation, indicating that the most likely cause of OCRL in this patient is the de novo translocation that disrupted the OCRL locus.

Adolescent

Galactosemia: alterations in sulfate metabolism secondary to galactose-1-phosphate uridyltransferase deficiency.

Cultures of nonmutant as well as galactokinase-deficient fibroblasts incorporate 20 percent more [35S]sulfate when galactose is substituted for glucose in the medium; galactose-1-phosphate uridyltransferase-deficient cells incorporate 65.5 percent less. In addition to incorporating less [35S]sulfate, the uridyltransferase-deficient cells showed significant accumulation of intracellular galactose-1-phosphate within 4 hours after galactose exposure. Under the same conditions, no difference in [3H]uridine incorporation was observed. This metabolic alteration, occurring in response to galactose exposure, may be related to the pathophysiology of classical galactosemia.

Cells, Cultured

Immunodepression in Taenia crassiceps infection: restoration of the in vitro response to sheep erythrocytes by activated peritoneal cells.

The in vitro response to sheep erythrocytes of mesenteric lymph node cells from mice infected with the larval cestode Taenia crassiceps is significantly depressed and can be restored to control levels by addition of activated peritoneal cells depleted of functional T or B lymphocytes. Adherent mesenteric lymph node cells from infected mice are unable to reconstitute the in vitro response to sheep erythrocytes of normal nonadherent cells. The responses of mesenteric lymph node cells from infected mice to the T-lymphocyte mitogens concanavalin A and phytohemagglutinin and the B-lymphocyte mitogen lipopolysaccharide are normal. Mesenteric lymph node cells from infected mice do not suppress the in vitro response to sheep erythrocytes of normal mesenteric lymph node cells. These results suggest that the immunodepression in T. crassiceps-infected mice is primarily the result of alterations in functional accessory cells.

Animals

The Philadelphia variant of galactokinase.

We have previously reported the existence of a polymorphism that causes black populations to have lower mean RBC galactokinase activity than comparable white populations. We have designated this allele the Philadelphia variant, GALKP, and have suggested that it is common in blacks and rare in whites. GALKP individuals have normal WBC GALK activity, in contrast to the half normal WBC GALK activities of heterozygotes for the allele (GALKG) that causes the galactokinase-deficient form of galactosemia. In one family, we have presented evidence for the existence of two sisters heterozygous for both GALKG and GALKP alleles. These individuals have 50% normal WBC GALK activity and less than 50% normal red cell activity. The latter finding indicates that the two variant GALK alleles additively affect RBC activity. The WBC results suggest that the low activity of GALK in RBC of individuals with the GALKP allele is due to its relative instability. We could obtain no evidence for such instability from studies of high reticulocyte bloods or RBC fractionation. Furthermore, we could not demonstrate that the GALK in WBC from GALKP individuals has altered electrophoretic migration.

Alleles