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Biomedical subjects

B J Lewis

Publications and source records attributed to B J Lewis.

15 recordsLinked to original sources

Comparison of procoagulant activities in extracts of normal and malignant human tissue.

Cancer procoagulant A (CPA) was originally described in extracts of tumor tissue, but whether this represented a quantitative and/or a qualitative difference from procoagulant activity in normal tissue extracts was not clear. Procoagulant activity was quantitated in extracts of 12 matched normal and malignant human tissue samples from the large intestine, breast, lung, and kidney. The specific activity of procoagulants in the tumor extracts was not greater than that in the extracts of normal tissue. Two enzymatic characteristics of CPA that distinguish it from tissue thromboplastin are its inhibition by diisopropylfluorophosphate (DFP) and its lack of dependence on factor VII. These specific tests were used to evaluate qualitative differences between procoagulants from normal and malignant intestinal tissues. In the paired normal and malignant tissue extracts, all tumor samples were inhibited by DFP and were active in factor VII-depleted bovine plasma (F7D-BP). In contrast, the extracts of normal tissue were insensitive to DFP and, except for one extract, were inactive in F7D-BP. Four of 9 other tumor extracts (44%) were positive for both of these tests for CPA, whereas the other 5 extracts were positive for only one of the two tests. The results suggest that extracts of normal and malignant tissues contained similar levels of procoagulant. However, malignant tissue contained a procoagulant enzymatically different from normal tissue thromboplastin. Furthermore, most of the malignant tissue extracts seemed to contain little or no thromboplastin.

Blood Coagulation Factors

The chemotherapy of Hodgkin's disease: past experiences and future directions.

From the standpoint of chemotherapy, the first progress in the treatment of Hodgkin's disease was the identification of the activity of nitrogen mustard in the 1940's. The initial antitumor effect of the drug created a great excitement. However, when all patients later relapsed, there was subsequent dejection and skepticism about the utility of drug therapy. Fortunately, in the 1950's and 1960's, the development of other effective agents (vinca alkaloids, corticosteroids, and methylhydrazines) in conjunction with the elucidation of the principles of combination chemotherapy led to a marked increase in the antitumor response rate of patients with Hodgkin's disease. The value of many of these drug combinations remains under study. Nonetheless, approximately 75% of all patients with advanced Hodgkin's disease treated today with combination chemotherapy can achieve a complete remission. In addition, over half of these remain disease-free long enough to be considered cured. The development of effective treatment, both local (radiotherapy) and systemic (MOPP chemotherapy), has given the clinical investigator the tools to complete, in the 1970's, the therapeutic experiments necessary to refine both the interrelationship between the treatments and their impact upon the natural history of Hodgkin's disease.

Antineoplastic Agents

A comparison of the 16S ribosomal RNAs from mesophilic and thermophilic bacilli: some modifications in the Sanger method for RNA sequencing.

Two modifications in the Sanger two dimensional electrophoretic procedure for RNA analysis are reported. One increases resolution on the primary fingerprint to the point that digests of large RNAs, of the size 1500-3000 nucleotides yield well resolved fingerprint patterns. The other is a novel endonucleolytic procedure that proves useful in determining sequences of the large oligonucleotides produced by T1 ribonuclease. These modifications have been used in determining the catalogs of oligomers produced by T1 ribonuclease digestion of 16S rRNAs from three related organisms, Bacillus subtilis, B.pumilus and B.stearothermophilus. The possible effects of adaptation to a thermophilic niche on ribosomal RNA primary structure and the phylogenetic relatedness of the two mesophilic Bacilli are discussed.

Animals

Lesions produced by human herpesviruses 1 and 2. Morphologic features in rabbit corneal epithelium.

The morphologic features of corneal lesions produced in rabbits by human herpesviruses, types 1 and 2 (HH1 and HH2), were studied using light and electron microscopic techniques. Also, healing lesions produced by the HH1 virus and treated by idoxuridine were similarly investigated. Scanning electron micrographs showed that although the morphology of HH1 and HH2 lesions was similar in most respects. HH2 lesions typically were raised, whereas the edges of HH1 lesions were not elevated above the corneal surface. In both HH1 and HH2 lesions, infected epithelial cells first separated from neighboring cells, then became globular, and finally were removed, leaving a central excavation. During healing of HH1 lesions, normal epithelial cells invaded the central crater from all sides to cover damaged cells and reconstitute the epithelial surface.

Animals

Ultrastructural study of lesions induced in rabbit cornea by Herpes Simplex virus types 1 and 2.

Herpes simplex virus types 1 and 2 were used to infect rabbit corneas (without abrasion), and the resulting lesions were compared by light and electron microscopy. The type 1-induced lesion developed more quickly; the infected epithelial cells underwent a progression of defined morphological changes leading to organelle destruction, cell rounding, and death. Virus particles were abundant in the nuclei and cytoplasm of all types of cell in the epithelium, in intercellular spaces, and on the basement membrane. Occasionally, virus was seen to replicate within stromal fibroblasts. In contrast, type 2, although causing similar changes in the epithelial cells, was relatively inefficient in the production of mature virions. Thus type 2 nucleocapsids were synthesized within nuclei in numbers comparable to those of types 1, but intact cytoplasmic virions were uncommon, apparently because of degradation of type 2 virions in cytoplasmic vesicles or tubules. Extracellular type 2 particles were rarely seen. This finding offers an explanation for the relatively slow development of the type 2-induced lesion, but not for its greater severity. All epithelial cells appeared to be capable of supporting replication of either type of virus.

Animals

Serological analysis of human deoxyribonucleic acid polymerases. Preparation and properties of antiserum to deoxyribonucleic acid polymerase I from human lymphoid cells.

The preparation and properties of an antiserum to human DNA polymerase I (6 to 8 S) are described. Care was taken in the purification of the antigen to remove certain other DNA polymerases found in human cells. An incubation of antigen and antiserum lasting about 48 hours is necessary to achieve maximal inhibition. About 1 mug of the antipolymerase immunoglobulin G, prepared in rats, neutralizes 60% of the activity present in 54 ng of the enzyme. Tritrations varying both antiserum and enzyme demonstrate clear regions of antigen and antibody excess. Inhibition of enzyme activity is about the same whether the templateprimer is (dA)n-(dT)12-18, or partially digested DNA. An assay was developed which measures the remaining activity in the supernatant after precipitation of enzyme-antibody complexes with goat anti-rat immunoglobulin G. In this assay, 2.2 mug of the antipolymerase immunoglobulin G quantitatively bind 33 ng of DNA polymerase I. With use of the direct neutralization assay and the immuno-precipitation test, we found little, if any, antigenic relationship between DNA polymerase I and DNA polymerase II (3.4 S). Similarly, little, if any, relationship was found to the DNA polymerases from five RNA tumor viruses. The activities of RNA-directed DNA polymerases from the blood leukocytes of two patients with acute myelogenous leukemia and from the placentas of rhesus monkeys were not inhibited in neutralization assays which were shortened because these enzymes were thermolabile. In identically shortened neutralization assays, the antipolymerase immunoglobulin G neutralized up to 76% of the activity of DNA polymerase I. In addition to its utility in distinguishing cellular DNA polymerases, the rat antiserum should be useful reagent for testing of novel DNA polymerases isolated in small quantities from human tumors for contamination with DNA polymerase I. This enzyme is present in abundance in proliferating tissue and often confuses the biochemical characterization of these novel enzymes.

Animals

Sensory deprivation in young children.

The importance of the role of intentional movement and active exploration in the development of a child's knowledge concerning his body, his movement and his surrounding is recognized. Senoristasis is defined and the concept applied to deprivation studies with animal and human subjects. It is suggested that the principle can be used to explain behavioural patterns found in two groups of children who may suffer from sensory deprivation; namely those who live in environments which provide insufficient stimulation and those who lack the necessary mobility to explore the environment in which they live. The importance in a young child's development of a rich sensory environment and opportunities for exploration are stressed.

Animals

Structuring movement experiences for pre-school children.

It is proposed that a conceptual framework should be used as a basis for the provision of movement experiences for young children. Developmental levels and classifications of movement are considered in order to structure environments that provide suitable opportunities for self-initiated movement for pre-school children.

Affect