PubMed Health⌕ Search

Biomedical subjects

S Brill

Publications and source records attributed to S Brill.

At least 19 recordsLinked to original sources
PubMed1992

The liver as a stem cell and lineage system.

We propose that the liver is a stem cell and lineage system with many parallels to lineages in the bone marrow, gut, and epidermis, varying from them only in kinetics. All are organized with three compartments: a slow cycling stem cell compartment with cells expressing a fetal phenotype and responding slowly to injury; an amplification compartment with cells of intermediate phenotype rapidly proliferating in response to regenerative stimuli or acute injuries; and a terminal differentiation compartment in which cells increasingly differentiate and gradually lose their ability to divide. In all systems, both those with slow or rapid kinetics, the various compartments are positioned in a polarized organization, are associated with a gradient in the chemistry of the extracellular matrix, and show lineage-position-dependent growth responses, gene expression, pharmacological and toxicological responses, and reaction to viruses and radiation. In general, known oncogens selectively kill cells in the differentiation compartment inducing chronic regenerative responses of the cells in stem cell and/or amplification compartment. Tumors arise by subsequent transformation of the activated stem cells or early precursor cells. The evidence for a lineage model consists of the data implicating gradients in cell size, ploidy, growth potential, and antigenic and gene expression in the liver parenchyma along the sinusoidal plates. The traditional explanation for this heterogeneity is that it represents adaption of cells to a changing sinusoidal microenvironment dictated by the direction of blood flow. However, we review the extant data and suggest that it more readily supports a lineage model involving a maturation process beginning with stem cells and precursors in the periportal zone and ending with sensescing parenchyma near the central vein. Support for this theory is provided by the studies on phenotypic heterogeneity in liver, investigations into the embryology of the liver, and analyses of the responses of liver to chemical and viral oncogens that induce rapid proliferation of small cells with oval-shaped nuclei, "oval cells," now thought to be closely related to liver stem cells. The lineage model provides clarity and insights into many aspects of liver biology and disease including the limited proliferative ability of in vitro parenchymal cultures, liver regeneration, gene expression, viral infection, hepatocellular carcinogenesis, liver cell transplantation, and aging.

Aging↗
PubMed1991

Bcr encodes a GTPase-activating protein for p21rac.

More than thirty small guanine nucleotide-binding proteins related to the ras-encoded oncoprotein, termed Ras or p21ras, are known. They regulate many fundamental processes in all eukaryotic cells, such as growth, vesicle traffic and cytoskeletal organization. GTPase-activating proteins (GAPs) accelerate the intrinsic rate of GTP hydrolysis of Ras-related proteins, leading to down-regulation of the active GTP-bound form. For p21ras, two GAP proteins are known, rasGAP and the neurofibromatosis (NF1) gene product. There is evidence that rasGAP may also be a target protein for regulation by Ras and be involved in downstream signalling. We have purified a GAP protein for p21rho, which is involved in the regulation of the actin cytoskeleton. Partial sequencing of rhoGAP reveals significant homology with the product of the bcr (breakpoint cluster region) gene, the translocation breakpoint in Philadelphia chromosome-positive chronic myeloid leukaemias. We show here that the carboxy-terminal domains of the bcr-encoded protein (Bcr) and of a Bcr-related protein, n-chimaerin, are both GAP proteins for the Ras-related GTP-binding protein, p21rac. This result suggest that Bcr could be a target for regulation by Rac and has important new implications for the role of bcr translocations in leukaemia.

Amino Acid Sequence↗
PubMed1989

Characterization of lympho-myeloid-erythroid-megakaryocytic stem cells in peripheral blood of hairy cell leukemia patients.

Circulating stem cells with lympho-myeloid-erythroid differentiative capacity have been described in the peripheral blood of hairy cell leukemia (HCL) patients (Michalevicz R. & Revel M. (1987) Interferons regulate the in vitro differentiation of multilineage lympho-myeloid stem cells in Hairy Cell Leukemia. Proc. natn. Acad. Sci. U.S.A. 84, 2307.) The aim of the present work was to enrich the progenitors and characterize their antigenic and growth properties. Peripheral blood (PB) from HCL patients was stained with antibodies (BI3C5 (CD34) and/or My10 as well as RFB7 (CD20) and RFT12 (CD7) and sorted using flow cytometry (FCM) into positive and negative fractions. Peripheral blood cells from several patients showed 4-16% cells positive for the BI3C5/My10. The positive fraction contained all the colony-forming cells and LGEM/LG/LGM colonies were enriched approximately ten-fold as compared to the unsorted population. No colony was found in the negative fraction. All colony forming cells were in the RFB7 and RFT12-negative fractions. Thus, circulating stem cells with lymphoid/myeloid potential can be isolated from PB of HCL patients.

Antibodies, Monoclonal↗
PubMed1987

Individual changes in T lymphocyte parameters of old human subjects.

Parameters of peripheral blood T lymphocytes were determined repeatedly (twice, 2-4 weeks apart), in ten old (78 + 5) and compared to nine young (31 + 5) human subjects. Assays included percentage of total, helper, and suppressor, T lymphocytes, and the reaction to PHA stimulation for 24, 48, 72, and 96 h, as assessed by levels of proliferation and IL-2 production. A lower response to PHA was observed in the old as compared to the young, with no significant changes in T cell subsets. A marked variability was noted between the results of the first and second determinations of the response to PHA in each individual. The lack of correlation between the two determinations was more prominent in the old. Unresponsiveness to PHA throughout the incubation period, was noted in two old subjects, but, in only one of the two determinations. This transient unresponsiveness was not accompanied by any changes in their clinical state. Thus, establishments of the immune status of the aged should be based on at least two repeated determinations.

Aged↗
PubMed1986

DNA-mediated transfer of cAMP resistance in CHO cells.

Chinese hamster ovary (CHO) strain 10215 carries a dominant mutation which confers resistant to cAMP by virtue of an altered catalytic subunit of the cAMP-dependent protein kinase (Evain et al., 1979). This mutation was transferred to wild-type CHO cells by DNA-mediated gene transfer. Based on the absence of cAMP growth inhibition, seven transformant colonies were isolated. One of these, 11586, was studied in detail. This transformant showed the same phenotype as the mutant, including resistance to the morphological changes and growth inhibitory effects of 1 mM 8-Br-cAMP, reduced total cAMP dependent protein kinase activity and lowered sensitivity of the kinase to cAMP activation. When the cAMP-dependent protein kinase was fractionated on a DEAE-cellulose column, the transformant was lacking in type II cAMP dependent protein activity, to the same degree as the mutant. The transformant and mutant, but not wild-type cells, also failed to phosphorylate a 52,000-dalton protein in a cAMP-dependent manner. These characteristics support the conclusion that the gene for the mutant cAMP-dependent protein kinase has been transferred. The ability to transfer this gene by DNA-mediated transfer suggests that this methodology may be useful for the molecular isolation of the gene encoding the catalytic subunit of cAMP-dependent protein kinase.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

High levels of a common anti-DNA idiotype (16/6), a genetic marker for SLE.

Six out of 8 healthy first-degree relatives of a patient with systemic lupus erythematosus (SLE) had very high serum levels of a common anti-DNA idiotype (16/6). In this family an additional sister developed SLE, and all members were heterozygous for C4 deficiency. Measurements of common autoantibody idiotypes may contribute to the understanding of the genetics of autoimmune diseases. They might be found useful in detecting healthy subjects prone to the development of an overt clinical state.

Autoantibodies↗
PubMed1985

DNA-mediated gene transfer of a mutant regulatory subunit of cAMP-dependent protein kinase.

We have used DNA-mediated gene transfer of genomic DNA to introduce into wild-type Chinese hamster ovary (CHO) cells a mutant gene that confers resistance to the growth inhibitory effect of cAMP. This dominant mutation in CHO cell line 10248 is responsible for an alteration in the RI subunit (RI*) of the type I cAMP-dependent protein kinase (Singh, T. J., Hochman, J., Verna, R., Chapman, M., Abraham, I., Pastan, I.H., and Gottesman, M.M. (1985) J. Biol. Chem. 260, 13927-13933). The transformant 11564 which was studied in detail, has the same characteristics as the original mutant 10248 including continued growth in medium containing 8-Br-cAMP, an increase in the Ka for cAMP activation of the kinase, a greatly reduced amount of type II protein kinase activity, an altered incorporation of the photoaffinity label 8-N3[32P]cAMP into the RI* subunit of PKI, and an absence of cAMP-dependent phosphorylation of a Mr = 52,000 protein in intact cells. In addition, analysis of the DNA of the transformant indicates the presence of an increased amount of DNA for the RI gene. These results are consistent with the transfer of a mutant gene for the RI* subunit of the cAMP-dependent protein kinase and its phenotypic expression in the transformant and also support the hypothesis that the mutation responsible for the defect in cell line 10248 is due to an alteration in the gene for RI.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Detection of cross-reactive anti-DNA antibody idiotypes in the serum of systemic lupus erythematosus patients and of their relatives.

Two common cross-reacting anti-DNA antibody idiotypes designated 16/6 and 32/15, previously identified in the serum of patients who have systemic lupus erythematosus, were found in 24% and 7%, respectively, of 147 first-degree relatives. These findings imply that high-frequency germ-line genes exist among lupus relatives, as well as patients. These dominant or public anti-DNA antibody idiotypes are not likely to be pathogenic factors, but are probably a genetically associated phenomenon.

Antibodies, Antinuclear↗
PubMed1985

Effect of food intake on exercise fatigue in trained and untrained subjects.

The effects of carbohydrate and fat intake on exercise-induced fatigue was investigated in 30 untrained--(VO2max of 40.6 +/- 2.7 ml X kg-1 X min-1) and 24 trained-subjects (VO2max of 52.3 +/- 2.7 ml X kg-1 X min-1) performing a 34 km march with a 25 kg backpack. Marching time was 8 1/2 h and 6 1/3 h in the untrained and trained-subjects respectively. The subjects were divided into 3 dietary groups. One group had free access to sugar cubes, the second group was offered almonds and the third one served as a control. Triglyceride levels decreased by 65 mg X dl-1 in untrained, and by 115 mg X dl-1 in trained subjects, while blood glucose remained at normal levels. In the untrained subjects, ingestion of almonds delayed the subjective sensation of exhaustion, while 50% of the controls and the sugar consuming subjects complained of exhaustion. The data suggest that ingestion of food containing fat delays exercise induced exhaustion or fatigue to a greater extent than does carbohydrate ingestion.

Adolescent↗
PubMed1985

Infant astigmatism and meridional amblyopia.

The orientation preferences of 70 infants aged 7 to 53 weeks with significant astigmatism [1.0 or more diopters (D)] were measured using a preferential looking procedure with paired gratings. The preference data show the consequences of the blurring effects of astigmatism when these are not compensatable by accommodation. Data from infant astigmats tested with optical correction look like those of nonastigmats. We have found no evidence for the development of meridional amblyopia during the first year of life.

Accommodation, Ocular↗
PubMed1985

Development of acuity and stereopsis in infants with esotropia.

Visual acuity and stereopsis of 19 esotropic infants and toddlers, 36 normal infants and 7 children with refractive anomalies were measured during the first three years of life using newly developed preferential looking procedures. Children with infantile esotropia corrected with prisms equal in size to the deviation show some degree of binocularity up to at least 21/2 years, as measured by a polaroid bar stereogram procedure with a 1800 seconds of arc disparity. A few children, who did not receive any therapeutic intervention, failed this test during the first and second year. However, all older subjects (over 6 years of age) with a history of infantile esotropia failed the test.

Adolescent↗
PubMed1985

Legionnaires' disease: new etiologic agents.

Two patients with pneumonitis due to legionellosis are described. The etiologic diagnosis was based on high titers of immunoglobulin (Ig)M class antibodies (1/2048 and 1/512) detected by indirect immunofluorescence. The etiologic agents were presumed to be Legionella bozemanii in one case and either L. bozemanii or L. longbeachae in the other. Both patients made an uneventful recovery. Infections with these organisms have not been described in Israel previously.

Aged↗
PubMed1985

The development of visual acuity in infant astigmats.

Acuity for vertical, horizontal, and oblique gratings was measured in 77 infant astigmats using a preferential looking procedure. Measurements were made with the refractive error uncorrected. Most of the infant astigmats were slightly to moderately hyperopic with respect to the test distance of 50 cm. Their acuity was not significantly different from that of a group of non-astigmatic infants. Average acuity for vertical and horizontal gratings increased from 6/200 at 1 month of age to 6/24 at 1 yr. Average acuity for oblique gratings increased more slowly, so that by 1 yr of age it was only 6/33. The only infants to show reductions in acuity were those with a strong myopic focus and one infant with a very strong hyperopic focus. When this infant was tested with optical correction, acuity improved to normal levels. This suggests that meridional amblyopia develops sometime after the first year of life or that it is confined to high spatial frequencies.

Astigmatism↗