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Biomedical subjects

R Allen

Publications and source records attributed to R Allen.

At least 217 records · Page 12Linked to original sources

omega-123I-hexadecanoic acid metabolic probe of cardiomyopathy.

The utility of omega-123I-hexadecanoic acid myocardial scintigraphy as a metabolic probe of cardiomyopathies was investigated. Sixteen patients with a variety of cardiomyopathies and myopathies that involve cardiac muscle and ten volunteers were imaged in the postabsorptive state in a 40 degrees LAO projection after a standard dose of omega-123I-hexadecanoic acid. An elimination T1/2 was calculated from the left ventricular myocardial time-activity curve. An uptake index, corrected for chest wall attenuation, was also computed in 7 of 10 volunteers and 8 of 16 patients. Of the 16 patients, only 2 had distinctly abnormal omega-123I-hexadecanoic acid myocardial tracer kinetics. The first patient had a metabolic disorder of which carnitine deficiency was one component. The second patient had endocardial fibroelastosis, a process which has been linked to disorders which deprive the myocardium of oxygen and energy. Therefore, the cardiomyopathy may have been caused by some abnormality of cardiac metabolism other than carnitine deficiency. Although of limited utility in the overall cardiomyopathic population, omega-123I-hexadecanoic acid myocardial scintigraphy should be further investigated as a screening test for carnitine deficiency and related metabolic abnormalities in patients at risk.

Adolescent↗

Beneficial effects from systematic dosage reduction of the diuretic, chlorthalidone: a randomized study within a clinical trial.

The purpose of this study was to determine the effects on blood pressure and selected biochemical measures of reducing the dosage of chlorthalidone from 100 mg to 50 mg. Within the larger study (Multiple Risk Factor Intervention Trial), 140 Special Intervention hypertensive men, taking 100 mg of chlorthalidone daily, were randomly assigned to either a continuation of 100 mg or a dosage reduction to 50 mg daily. Men were followed monthly for 4 months. Measures were made of blood pressure, serum potassium, serum uric acid, serum glucose, serum cholesterol, and triglycerides. Blood pressure change from baseline to 4 months revealed a significantly higher diastolic blood pressure in the group continued on the 100 mg dose compared to the dose reduction group. However, analysis of covariance, which took into account baseline differences in blood pressure, resulted in a nonsignificant difference in follow-up blood pressure (systolic and diastolic) between groups. Serum potassium increased significantly in the dose reduction group, especially in those participants taking supplemental potassium chloride. The results of this study demonstrate that a reduced dose of 50 mg chlorthalidone over the 4-month period was as effective as the 100 mg dose in long-term, well-controlled hypertensive men. Careful study of other antihypertensive agents is warranted to determine the drug dose that is maximally effective for blood pressure lowering and that also minimized toxic and adverse effects.

Blood Glucose↗

Origins of language delay in abused infants.

This paper presents a reanalysis of data collected in a study of abusing mother-infant pairs, emphasizing the failure of infants with a history of physical abuse to develop appropriate language skills. Bayley Mental Development indices of abused infants decreased with age. This decrease was attributable largely to the failure of abused infants to pass verbal items. None of the abused children had any verbal communication skills. Results are discussed in relation to patterns of maternal ignoring and lack of verbal stimulation.

Age Factors↗

DATALIN--an interactive data entry program for use with NONLIN.

A package of FORTRAN programs for data entry into NONLIN (version II) is described which may be used in the analysis of plasma-concentration time curves after single or multiple doses for fourteen pharmacokinetic models described in terms of the model's microconstants (volume of compartments, rate constants). In all cases, infusion rates must be zero-order and absorption rates first-order. The program contains an edit subroutine allowing for changes in initial parameter estimates and their lower and upper limits, weighting factors, number of iterations in the NONLIN analysis, and plot option. Individual X and Y values may be changed and listed and X-Y data pairs may be inserted or deleted. Factors pertaining to each of the data entries in relation to NONLIN are discussed.

Animals↗

Maternal withdrawal from handicapped toddlers.

Videotaped observations of the free-play interaction of mothers and (a) 12 physically handicapped, (b) 14 premature and (c) nine healthy 2-year-olds were evaluated. Mothers of handicapped toddlers were significantly more likely to ignore their children at 24 months than were mothers in other groups. Further, although children's Bayley scores had not differed when seen previously at 1 year, children of mothers who ignored at 2 years had lower concurrent 2-year IQ scores and experienced an average 30-point drop between the two evaluations. These results support clinical reports of maternal withdrawal from handicapped young children and suggest that the mother-child dyad in such cases may be at continuing risk throughout the early years.

Child, Preschool↗

Demonstration and partial characterization of the interferon-gamma receptor on human mononuclear phagocytes.

Radioiodinated recombinant human interferon-gamma (IFN gamma) bound to human monocytes, U937, and HL60 cells in a specific, saturable, and reversible manner. At 4 degrees C, the different cell types bound 3,000-7,000 molecules of IFN gamma, and binding was of comparable affinity (Ka = 4-12 X 10(8) M-1). No change in the receptor was observed after monocytes differentiated to macrophages or when the cell lines were pharmacologically induced to differentiate. The functional relevance of the receptor was validated by the demonstration that receptor occupancy correlated with induction of Fc receptors on U937. Binding studies using U937 permeabilized with digitonin showed that only 46% of the total receptor pool was expressed at the cell surface. The receptor appears to be a protein, since treatment of U937 with trypsin or pronase reduced 125I-IFN gamma binding by 87 and 95%, respectively. At 37 degrees C, ligand was internalized, since 32% of the cell-associated IFN gamma became resistant to trypsin stripping. Monocytes degraded 125I-IFN gamma into trichloroacetic acid-soluble counts at 37 degrees C but not at 4 degrees C, at an approximate rate of 5,000 molecules/cell per h. The receptor was partially characterized by SDS-polyacrylamide gel electrophoresis analysis of purified U937 membranes that had been incubated with 125I-IFN gamma. After cross-linking, the receptor-ligand complex migrated as a broad band that displayed an Mr of 104,000 +/- 18,000 at the top and 84,000 +/- 6,000 at the bottom. These results thereby define and partially characterize the IFN gamma receptor of human mononuclear phagocytes.

Cell Differentiation↗

Successful chemotherapy for cystosarcoma phyllodes in a young woman.

Cystosarcoma phyllodes is a rare neoplasm of the breast. The tumor contains both stromal and epithelial elements. Local excision or simple mastectomy is usually curative. Most recurrences are local and can be controlled with excision. We treated a 23-year-old woman in whom disease had metastasized to the lungs with six courses of doxorubicin hydrochloride and cisplatin at three-week intervals and achieved complete remission.

Adult↗

The behavioral development of physically handicapped children in the second year.

Studies of school-aged children with physical handicaps often report cognitive-linguistic deficits, passivity, and inhibition. This study has attempted to determine whether this pattern is anticipated in earlier developmental periods, by examining the functioning of toddlers with physical anomalies (but without CNS damage) compared to premature toddlers (who share some aspects of deviant early experience) and to normal toddlers. Fourteen infants in each group were videotaped, longitudinally, at 9, 12, 18, and 24 months, in interaction with their mothers and in various semistructured situations. Developmental level was assessed at 12 months (Bayley scales) and at 24 months (Stanford-Binet IQ). Both groups of at risk toddlers performed more poorly in measures of focused play, language production, social initiative, affective expression, and 2-year IQ. Handicapped toddlers were more distractible, less compliant, and less willing to separate from their mothers, than were prematures. Patterns previously described for older handicapped children can therefore be recognized as early as the second year of life.

Child Development↗

At-risk toddlers and their mothers: the special case of physical handicap.

Previous studies of school-aged children with physical handicaps indicate passivity, inhibition, and deficits in cognitive-linguistic functioning, sometimes interpreted as consequent to parent-child problems. The present study examined the functioning of toddlers with physical anomalies (but without CNS damage) in comparison to premature toddlers (who share deviant early experience but not deviant physical appearance) and to normal toddlers. 14 mother-child pairs in each group were videotaped at 9, 12, 18, and 24 months in a variety of semistructured situations. Both premature and handicapped toddlers performed more poorly in measures of social initiative, focused play, language production, and 2-year IQ. In addition, handicapped toddlers manifested increased distractibility, decreased compliance, and reluctance to separate from their mothers. Mothers of both prematures and handicapped toddlers were more initiating and less responsive than controls, while mothers of handicapped children were also more likely to both encourage and ignore their toddlers. Patterns previously reported for older children are therefore found here with toddlers. Maternal patterns are interpreted as supporting Bell's model of compensatory "lower-limit" effects.

Child Behavior↗

Two monoclonal antibodies selective for human mammary carcinoma.

Mouse myeloma cells were fused with spleen cells from BALB/c mice immunized with the MCF-7 human mammary carcinoma cell line. Among hybridomas, two (3B18 and 15A8) were selected and cloned. Hybridoma 3B18 produces kappa-IgG1 antibodies that react with a cytoplasmic component of MCF-7 cells. In immunoperoxidase assays, 3B18 reacts with 27 of 31 specimens of human mammary carcinoma. It reacts most consistently with poorly differentiated and infiltrating ductal breast cancers, but it also reacts with isolated cells in 3 of 5 benign mammary pathological lesions with a variable distribution. The antibody does not react with normal mammary epithelium. It does not react with any normal human tissues, and it reacts with only one of 19 other cancers tested. Hybridoma 15A8 produces kappa-IgG1 antibodies that react with the surface membranes of the cells of two human breast cancer cell lines but not with a human fibroblast cell line. In immunoperoxidase assays, the antibody reacted with 28 out of 31 human mammary carcinomas. The antibody also reacts more weakly with normal human epithelial cells of breast, renal proximal tubule, skin, esophagus, and salivary gland, but no other normal tissue. The antibody was unreactive with 14 of 18 other malignant tissues tested. Since 3B18 and 15A8 detect antigens found predominantly in human mammary carcinomas and, possibly, distinguish overlapping categories of human mammary carcinomas, they may prove useful in determining the cellular lineage from which human mammary carcinomas arise, or they may have other clinical applications in breast cancer.

Antibodies, Monoclonal↗

Sequence analysis of ultraviolet-induced mutations in M13lacZ hybrid phage DNA.

We have studied the specificity of ultraviolet (u.v.) mutagenesis in single-stranded DNA phage by analyzing u.v.-induced forward mutations in the lac insert of M13mp2 hybrid phage. Sequence analysis of 114 lac mutants derived from u.v.-irradiated phage grown in u.v.-irradiated cells showed that ultraviolet induces mainly single-nucleotide substitutions and deletions in progeny phage DNA. A total of 74% of the single-base substitution mutations occurred at sites of adjacent pyrimidines in the single-stranded DNA, with both T----C and C----T transitions predominating in the u.v. spectrum. Single-nucleotide deletion mutations occurred preferentially in tracts of repeated pyrimidine nucleotides. Tandem, double-base substitutions did not represent a major class of u.v.-induced mutations, but nearly 10% of mutant clones contained multiple, non-tandem nucleotide changes.

Base Sequence↗

Microvillin: a 200-kilodalton protein in microvilli of rat mammary cells detected by a monoclonal antibody.

We have isolated a monoclonal antibody that was raised against rat mammary tumor cells. The antibody stains the lumenal edge of mammary duct epithelial cells. It immunoprecipitates a 200-kilodalton nonglycosylated, nonphosphorylated protein, which, by immunofluorescence and electron microscopy, can be localized in microvilli. In addition to microvilli of mammary ducts, this monoclonal antibody stains microvilli of the salivary ducts and of the renal nephron. It does not stain the microvilli of the intestinal brush border and shows a different tissue distribution than previously described proteins of this microvillus. We propose the name microvillin to distinguish the protein from other microvillar proteins. The presence of the protein distinguishes two classes of microvilli that are present in cells with possibly different transport functions.

Animals↗

Developmental regulation of cytokeratins in cells of the rat mammary gland studied with monoclonal antibodies.

We have isolated two monoclonal antibodies to cytokeratins and determined their cell specificities. They display interesting localization within the rat mammary gland. One (1A10) shows specificity for myoepithelial cells; the other (24B42) is specific for lumenal cells at various stages of development. These two monoclonal antibodies and three others to cytokeratin previously isolated were used in conjunction with antibodies to myosin and collagen IV to confirm and extend our previous findings on epithelial cell types and development within the mammary gland.

Aging↗

The medial gastrocnemius muscle flap: a local free flap.

A new application of the medial gastrocnemius muscle flap has been described. Lengthening of the sural vascular pedicle was obtained using interposition vein grafts. This allowed coverage of a larger defect than that which could have been obtained with the tethered muscle and without further insult to the already disturbed lower extremity anatomy. The principle of pedicle lengthening can be used to increase the arc of rotation of various other muscle, myocutaneous, skin, or bone flaps and thereby increase their usefulness.

Adult↗

Replication of endogenous avian retrovirus in permissive and nonpermissive chicken embryo fibroblasts.

Clones of chicken embryo fibroblasts exogenously infected with the endogenous avian retrovirus were analyzed to examine the replication of this virus in permissive (Gr+) and nonpermissive (Gr-) cells. The results demonstrate that the endogenous virus was capable of infecting both Gr+ and Gr- cells with equal efficiency. Infected clones of Gr+ and Gr- cells differed, however, in two significant ways. At the time of their initial characterization, the Gr+ clones produced 100- to 1,000-fold more virus than the Gr- clones. Further, the amount of virus produced by Gr+ clones did not change significantly during serial passage of the cells. In contrast, continued passage of the infected Gr- clones resulted in a gradual increase in the amount of virus produced. Individual clones of infected Gr- cells produced infectious virus at rates that, initially, differed by a factor of more than 10(4). The large differences in the production of virus by these clones could not be explained by equally large differences in the number of infected cells within the clonal populations. Greater than 80% of the clonal populations examined ultimately produced virus at rates that were not significantly different from the rates observed in infected Gr+ cells. Virus produced by these infected Gr- cells exhibited the same restricted replication upon establishing a new infection in nonpermissive cells. Analysis of the appearance of free and integrated viral DNA sequences during endogenous virus infection of Gr+ and Gr- cells demonstrated that, after an initial delay in the synthesis of free viral DNA in Gr- cells, the nonpermissive cells ultimately acquired as many integrated viral DNA sequences as were found in infected Gr+ cells. These results indicate that a majority of the infectious particles of the endogenous virus are capable of establishing infection in a Gr- cell and, ultimately, of producing virus at a rate that is not significantly different from that produced by infected Gr+ cells. The virus produced from the Gr- cells is not a stable genetic variant of the original endogenous virus that is capable of unrestricted replication in nonpermissive cells. The reduced efficiency with which the endogenous virus initially replicates in nonpermissive cells and the increased length of time required for infected Gr- cells to produce maximal virus titers suggest that the endogenous virus may utilize a different mechanism of replication in Gr+ and Gr- fibroblasts.

Alpharetrovirus↗