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Biomedical subjects

C A Miller

Publications and source records attributed to C A Miller.

At least 199 records · Page 11Linked to original sources

Differentiation stages of human natural killer cells in lymphoid tissues from fetal to adult life.

Virtually all human granular lymphocytes expressed the HNK-1 differentiation antigen when examined in lymphoid compartments from adults, neonates, and fetuses. The HNK-1+ cells were distinguishable into three subsets having distinct antigenic phenotypes: HNK+T3-M1-, HNK+T3+M1-, and HNK+T3-M1+. Thus, greater than 70% of the HNK-1+ cells from 13-17 wk fetuses (less than 0.2% of nucleated cells) lacked T cell antigens (e.g., T3, T8, T4, and T6) and the M1 myeloid antigen. Morphologically, the HNK+T3-M1- cells consisted of three different types: small granular lymphocytes (less than 10% of HNK-1+ cells), agranular small lymphocytes with a narrow rim of cytoplasm (70-80%), and agranular giant cells (greater than 15 micrometers) with considerable neutrophilic cytoplasm (15%). The purified fetal HNK-1+ cells exhibited a low level of cytotoxicity against K562 target cells. On the other hand, almost all of HNK-1+ cells in neonatal tissues as well as adult bone marrow, lymph node, and thymus, exhibited the HNK+T3+M1- phenotype, contained sparse cytoplasmic granules, and had an intermediate level of NK functional activity. Only adult blood and spleen contained a majority of mature HNK-1+ cells. These cells had an HNK+T3-M1- phenotype, abundant cytoplasmic granules, and maximum NK function. We propose that human NK cells may generate from a separate cell lineage and that they alter their phenotype, morphology, and functional capability during differentiation.

Antigens, Surface↗

Nucleotide sequence of the partition locus of Escherichia coli plasmid pSC101.

We report here the sequence of a 375-bp EcoRI-AvaI DNA fragment that previously has been shown to contain a locus (termed partition or par) responsible for stable maintenance of the pSC101 plasmid in growing cell populations. The DNA sequence of the par region encodes no obvious proteins and contains no segments having the structural characteristics of transcriptional or translational start signals. However, segments of the par locus appear capable of forming regions of intra-strand secondary structure, one of which resembles a rho-independent transcription terminator. Computer analysis shows regions within par that have homology with sequences found near the origin of replication of the Escherichia coli chromosome and of the pBR322 and ColE1 plasmids. The par sequence homology in the pBR322 and ColE1 plasmids maps in the vicinity of sites that interact with the E. coli replication factor Y and accomplishes initiation of DNA synthesis on single-strand templates.

Base Sequence↗

Monoclonal antibody cross-reactions between Drosophila and human brain.

A panel of 146 monoclonal antibodies (MAbs), obtained with Drosophila melanogaster tissue as primary immunogen, was tested for cross-reactivity with the human central nervous system. Sites examined included spinal cord, cerebellum, hippocampus, and optic nerve. Nonnervous tissues tested were liver and lymph node. Approximately half of the antibodies reacted with one or more sites in the human central nervous system, identifying regional, cell class, and subcellular antigens. Some recognized neuronal, glial, or axonal subsets. Immunoblot analysis revealed that some antibodies reacted with similar antigen patterns in both species.

Adult↗

Monitoring and assessment in maternal and child health: recommendations for action at the state level.

Recent administration-sponsored changes in federal health policy and funding may harbor adverse effects for the health of mothers and children, and for the capabilities of state-level programs to serve them appropriately. Careful monitoring is required to assess the nature, extent, and impact of those changes. This paper examines several monitoring efforts in maternal and child health and recommends additional action at the state level to meet urgent information requirements.

Child↗

Interleukin 2 receptor expression by activated HNK-1+ granular lymphocytes: a requirement for their proliferation.

A subpopulation of HNK-1+ cells was found to express interleukin 2 receptor (IL 2R) as monitored by the anti-Tac monoclonal antibody after lectin or allogeneic cell stimulation. When blood mononuclear cells were stimulated with phytohemagglutinin (PHA) or concanavalin A for 3 days, or with pokeweed mitogen or allogeneic mononuclear cells for 6 days, virtually all of the HNK-1+ cells remained as small resting lymphocytes. One-fourth of these HNK-1+ cells expressed IL 2R, however, usually within 18 hr after stimulation. Neither circulating HNK-1+ cells nor unstimulated HNK-1+ cells in short-term culture expressed IL 2R. Only the subset of HNK-1+ cells that expressed T cell surface markers, such as the sheep erythrocyte receptor and Leu-4 antigen, could be induced to express IL 2R. When long-term cultures of HNK-1+ cells were established with initial PHA stimulation and the continued presence of IL 2, a majority of the cells was found to express the IL 2R. When anti-Tac antibody was added to the long-term cultures, proliferation of the HNK-1+ cells was completely inhibited. These results suggest that entry into growth cycle by this subpopulation of HNK-1+ granular lymphocytes may require two signals: a relatively nonspecific ligand interaction with cell surface glycoprotein(s) to induce expression of IL 2R, and subsequent IL 2 interaction with these specific cell surface receptors.

Adult↗

Cell surface proteins and glycoproteins from biologically different human colon carcinoma cell lines.

Six cultured human colon cancer cell lines possessing different biological characteristics were enzymatically radiolabeled in situ with 125I and 3H, and the labeled cell surface proteins and glycoproteins were compared. The electrophoretic patterns of labeled cell surface material suggest correlations between biological properties and cell surface proteins. Highly aggressive cell lines (as assessed by in vitro parameters) had predominant peaks of 125I-labeled proteins between molecular weights 66,000 and 92,500. The major peak of radioiodinated material from the more indolent cell lines occurred between molecular weights 31,000 and 45,000. The profile of one 125I-labeled intermediately aggressive cell line was similar to the profiles of the more aggressive lines, whereas another intermediate line exhibited a profile different from those of both indolent and aggressive lines. Electrophoresis of tritiated material indicated that essentially all of the recovered labeled glycoprotein was of relatively high molecular weight (92,000-180,000) in the indolent lines, whereas the intermediate and highly aggressive lines had patterns with significant peaks between molecular weights 45,000 and 92,500.

Cell Line↗

Degree of lateralization as a hierarchy of manual and cognitive skill levels.

Four handedness measures and two cognitive measures were employed with 71 children aged from 3 to 10 yr. Results indicate that high-skill manual tasks become increasingly lateralized and low-skill manual tasks remain in their original, non-lateralized state. High-skill manual task performance correlated significantly with performance on the cognitive measures. Lateralization appears to be directly related to the skill level of the task, for both manual and cognitive tasks.

Child↗

Structure-activity correlations of cytochalasins. Novel halogenated and related cytochalasin C and D derivatives.

A series of halogenated and related analogues of cytochalasin C (CC) and D (CD) has been synthesized, and the biological activities of the analogues as inhibitors in a cell-free contractility model system obtained from Ehrlich ascites tumor cells were evaluated. The reaction sequence involved treatment of CD with phenyltrimethylammonium perbromide to give 6,12-dibromo-CD (2), dehydrohalogenation of 2 to 12-bromo-CC (3), and the subsequent conversions of 3 to 12-azido- (4), 12-iodo- (5), and 12-cyano-CC (6). The ID50 values for 5, 3, 4, 2, and 6 are 6.0, 7.4, 8.8, 45, and 77 X 10(-7) M, respectively, in comparison to ca. 2.8 X 10(-7) M for the parental compounds. The potential cell and molecular biological applications of these compounds are delineated.

Animals↗

Reversible repression and activation of measles virus infection in neural cells.

Conversion of acute measles virus infection to an indolent state has been achieved by treatment of infected cells of neural origin with agents that affect cyclic nucleotide metabolism. Striking results were obtained with papaverine, an inhibitor of cAMP phosphodiesterase that is capable of enhancing neural differentiation. In papaverine-treated cultures, decreased production of infectious virus was accompanied by selective disappearance of intracellular matrix proton, as detected by immunofluorescence. Viral nucleocapsid protein was enhanced in the cytoplasm while three other structural proteins--polymerase, hemagglutinin, and fusion protein--showed little change in distribution or intensity of staining. These results were specific for cells of neural origin and not observed in CV-1 or Vero cultures. cAMP, dibutyryl cAMP, 8-bromo-cAMP, and isobutylmethylxanthine all inhibited replication of virus but less so than did papaverine. Inhibition of virus replication by any of these agents was rapidly reversible, either by removal of the agent or by addition of cGMP to the culture medium and was accompanied by reappearance of the matrix protein. These results suggest that measles virus replication in neural cells depends on host factors, particularly those affecting endogenous cAMP and cGMP. Viral persistence may thus be related to the state of neural differentiation. This model system may yield information on mechanisms of recrudescence observed in some chronic diseases of the nervous system.

Animals↗

A clinical pathologic reappraisal of kernicterus.

Kernicterus at autopsy, traditionally associated with hyperbilirubinemia, is now often observed in the absence of markedly elevated levels of serum bilirubin. Attempts to document clinically predictive risk factors for kernicterus have been largely unsuccessful in the current population of sick neonates. In a study of 32 pairs of newborns with and without kernicterus at autopsy and matched for gestational age, weight, length of survival, and year of birth, no differences were found when multiple clinical factors thought to potentiate risk for kernicterus were compared. Microscopic sections of brains from these matched pairs were then evaluated without knowledge of the clinical or gross findings according to prearranged criteria. Statistic analysis of the microscopic findings was done, comparing each observed change in each anatomic site, all changes in each site, and each change in all sites. Although the gross pattern of staining followed that of classic kernicterus, the expected, specific histologic changes characteristic of kernicterus were found in only three patients. Spongy change, or edema, was significantly more common in the grossly stained brains (P less than .0005), but other findings were similar in both groups. Gross bilirubin staining of the neonatal brain with neither hyperbilirubinemia nor specific microscopic changes is probably not the same clinicopathologic entity as classic kernicterus.

Birth Weight↗

Inhibition of histidine decarboxylase by imidazole derivatives.

A series of 4-imidazolylmethyl arylsulfides, sulfoxides, and sulfones and two carbon isosteres of 4-imidazolylmethylphenyl sulfide (I) were synthesized and tested for inhibition of histidine decarboxylase from rat stomach. None of these analogs of I met the criterion of a potent and specific inhibitor of histidine decarboxylase.

Carboxy-Lyases↗

Demyelination with hemophagocytic lymphohistiocytosis of the CNS.

A case of hemophagocytic lymphohistiocytosis with central nervous system involvement in an infant is presented. Marked demyelination of cerebral and cerebellar white matter is associated with an intense histiocytic infiltrations and astrogliosis. Histiocytes phagocytic of erythrocytes and lymphocytes are noted in a meningeal, subependymal, and perivascular distribution. Severe depletion of lymphoid tissue, associated with histiocytic infiltration, is also seen in multiple organs. While the etiology of this disease is unknown, alterations in the immune response and possible viral relationships are explored.

Brain↗