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Biomedical subjects

J H Phillips

Publications and source records attributed to J H Phillips.

At least 181 records · Page 10Linked to original sources

Human thymic and peripheral blood non-MHC-restricted cytotoxic lymphocytes.

We propose that non-MHC-restricted cytotoxicity is mediated by two distinct types of lymphocyte: NK cells and a unique subset of cytotoxic T-lymphocytes (CTLs). Herein, we review experimental data to support the hypothesis that NK cells and non-MHC-restricted CTLs use different recognition structures and arise from distinct lineages. Furthermore, we demonstrate that non-MHC-restricted CTLs can be generated in vitro by culturing thymocytes in recombinant interleukin-2 (rIL-2).

Cytotoxicity, Immunologic↗

Plasmodium berghei: histology, immunocytochemistry, and ultrastructure of the placenta in rodent malaria.

The pathological changes associated with malarial infection in pregnancy were studied in rats and mice infected with Plasmodium berghei at different stages of gestation. Histopathological and ultrastructural studies of infected placentae near term in both species revealed disruption of architecture with gross thickening and necrosis of cells in the labyrinthine zone and fibrosis of the trilaminar trophoblast separating the maternal and fetal circulations. In the mouse, the extent of histopathological alterations in infected placentae ranged from the presence of immature erythrocytes in the fetal circulation in low grade maternal infection, to the marked deposition of fibrinoid material on the trilaminar trophoblast and inflammatory masses in severely infected placentae. In the rat, histopathological aberrations in the placentae were marked by placental stroma edema, fibrosis, and cellular infiltration. Immunohistological studies of cryostat sections of placentae from infected animals showed more parasites and pigment in infected mouse placentae than in the corresponding rat organ, but in both species parasites and pigment were largely confined to the maternal blood spaces and were only occasionally found in necrotic areas of trophoblast. No clear differences were observed between infected and control placentae in terms of the amount of IgG, IgM, or IgA which were each present in various amounts. These observations and the rarity of congenital malaria in the animals indicate that the placenta constitutes a major barrier to infection of the fetus. However, the pathological aberrations in the infected placentae may impose a biochemical stress upon the fetus which may account for the low birthweight, the increased frequency of abortion, and the greatly increased maternal and fetal death rates observed in malaria.

Animals↗

A neuroendocrine tumor of the small intestine with a karyotype of 46,XY,t(11;22).

Direct preparations of cells from a neuroendocrine carcinoma of the small intestine reveal a karyotype of 46,XY,t(11;22)(q25;q12). Though only 13 cells could be analyzed from both direct and 24 hour preparations, all revealed the translocation; no normal cell line was seen. The patient had not been treated at the time of biopsy. A similar translocation recently has been reported in a number of cases of Ewing's sarcoma and in peripheral neuroepithelioma. This common occurrence, along with the observation that a rearranged chromosome #22 with breakpoints at q11 or q12 are observed in other neoplasias including leukemia, suggests a possible causative role for these phenomena.

Carcinoma↗

Exercise-induced chronic compartment syndrome of the first dorsal interosseous muscle of the hand: a case report.

A 21-year-old welder experienced chronic pain in the region of the first dorsal interosseous muscle after strenuous activity involving his hand. Direct measurement of the tissue pressures within the first dorsal interosseous muscle revealed an elevation of compartment pressure after lateral key pinch activity. After surgical release of the compartment, the pressures returned to normal, and the patient's symptoms improved. Exercise-induced chronic compartment syndrome of the small muscles of the hand should be considered in patients who describe aching pain in the hand after strenuous activity.

Adult↗

Hair loss. Common congenital and acquired causes.

Hair loss is a common problem likely to be encountered by a clinical practitioner. The most frequent causes of hair loss in pediatric patients include tinea capitis, alopecia areata, traction alopecia, and trichotillomania. In the adult population, causes to be considered are alopecia areata and hair loss associated with systemic disease and hormonal influence. The clinician must be able to separate the types and causes of hair loss into those that reflect primary dermatologic conditions and those that represent reaction to systemic disease.

Adolescent↗

Antigenic, functional, and molecular genetic studies of human natural killer cells and cytotoxic T lymphocytes not restricted by the major histocompatibility complex.

Cytotoxicity not restricted by the major histocompatibility complex (MHC) is mediated by two distinct types of lymphocyte: natural killer (NK) cells and non-MHC-restricted cytotoxic T lymphocytes (CTL). These two types of cytotoxic lymphocytes can be distinguished by antigenic phenotype, function, and molecular genetic studies. In human peripheral blood, NK cells are identified by expression of the Leu-19 and/or CD16 cell surface antigens, and lack of CD3/T cell antigen receptor (Ti) complex expression (i.e., CD3-,Leu-19+). Peripheral blood non-MHC-restricted CTL express both CD3 and Leu-19 (i.e., CD3+, Leu-19+, referred to as Leu-19+ T cells). Both Leu-19+ T cells and NK cells lyse "NK-sensitive" hematopoietic tumor cell targets, such as K562, without deliberate immunization of the host. However, most "NK activity" in peripheral blood is mediated by NK cells, because they are usually more abundant and more efficient cytotoxic effectors than Leu-19+ T cells. The cytolytic activity of both NK cells and Leu-19+ T cells against hematopoietic targets was enhanced by recombinant interleukin 2 (rIL 2). NK cells, but not peripheral blood Leu-19+ T cells, were also capable of lysing solid tumor cell targets after short-term culture in rIL 2. Southern blot analysis of NK cells revealed that both the T cell antigen receptor beta-chain genes and the T cell-associated gamma genes were not rearranged, but were in germ-line configuration. These findings indicate that NK cells are distinct in lineage from T lymphocytes and do not use the T cell antigen receptor genes for target recognition.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, T-Lymphocyte↗

Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen).

A subset of peripheral blood T lymphocytes coexpressing CD3 and IgG Fc receptors (FcR) (CD16/Leu-11 antigen) have been identified, isolated, and functionally characterized. The CD3+, CD16+ cells were established in short-term culture using growth medium containing interleukin 2 (IL-2). Both the freshly isolated cells and the cultured cell line stably expressed the CD3+, CD16+ phenotype. Furthermore, a majority of these T cells lacked either CD4 or CD8 expression. Like in vitro-activated cytotoxic T lymphocytes and natural killer (NK) cells, the CD3+, CD16+ cells showed numerous azurophilic granules. Although these cells failed to mediate significant levels of NK cell-mediated cytotoxicity even after stimulation with IL-2, they efficiently functioned as effectors of antibody-dependent cellular cytotoxicity (ADCC). The Ig isotype specificity of the ADCC was analyzed using an isotype switch-variant family of a murine anti-HLA monoclonal antibody (mAb). Similar to the CD3-, CD16+ NK cell population, the CD3+, CD16+ T cells preferentially used the IgG2a antibody to mediate ADCC. The CD3+, CD16+ cells demonstrated a proliferative response when cocultured with either a NK-sensitive tumor cell line, K562, or a NK-insensitive B lymphoblastoid cell line, CCRF-SB. The response against CCRF-SB was significantly inhibited by anti-IL-2 receptor antibody, whereas the response against K562 was only partially diminished. Cytotoxicity was also induced in the CD3+, CD16+ population by the presence of anti-CD3 mAb, indicating that cytotoxicity can be triggered by stimulation via the CD3-T cell antigen receptor complex. By isolating these CD3+, CD16+ cells from the peripheral blood of a normal, healthy individual, it has been possible to extensively study the morphology, antigenic phenotype, and functional behavior of this unique subset of T lymphocytes expressing IgG FcR.

Antigens, Surface↗

A model for the differentiation of human natural killer cells. Studies on the in vitro activation of Leu-11+ granular lymphocytes with a natural killer-sensitive tumor cell, K562.

A subpopulation of low density granular lymphocytes that express the natural killer (NK) cell-associated Leu-11 antigen (IgG Fc receptor) were stimulated directly by coculture with an NK-sensitive tumor cell, K562. T lymphocytes (Leu-11-) responded only weakly when cocultured with K562. The response of Leu-11+ cells apparently did not require exogeneous factors or accessory cells. The K562-activated cells retained expression of Leu-11 antigen, acquired activation antigens, and were highly cytotoxic against NK-sensitive and -insensitive tumor cells. Anti-IL-2 receptor monoclonal antibody minimally inhibited the activation of Leu-11+ cells by K562, but completely inhibited the phytohemagglutinin-induced activation of the Leu-11- cells from the same individual. Leu-11+ cells can be divided into Leu-7-11+ and Leu-7+11+ subpopulations using anti-Leu-7 antibody. These subsets were separated by two-color fluorescence-activated cell sorting and cocultured with K562. Proliferation by Leu-7-11+ cells was significantly greater than by Leu-11+7+ cells. Leu-7+11- granular lymphocytes and T lymphocytes (Leu-7-11-) typically proliferated only weakly when cocultured with K562. A proportion of the Leu-7-11+ cells acquired Leu-7 antigen after stimulation with K562, whereas the phenotype of Leu-7+11+, Leu-7+11-, and Leu-7-11- subsets was unaffected. These results demonstrate a developmental relationship between the Leu-7-11+ and Leu-7+11+ lymphocytes and suggest that Leu-7 antigen may be expressed late in the differentiation pathway of NK cells. The direct activation of highly purified Leu-11+ cells by coculture with K562 provides an in vitro model with which to study the activation and maturation of human NK cells.

Antibodies, Monoclonal↗

Glycoproteins of the chromaffin-granule matrix: use of lectin blotting to distinguish several separate classes.

The soluble proteins released by hypotonic lysis of highly purified bovine adrenal chromaffin granules were analysed by one- and two-dimensional electrophoresis, followed by transfer to nitrocellulose and decoration with lectins or specific antibodies. The effects of neuraminidase treatment, and of chemical deglycosylation by trifluoromethanesulphonic acid, were investigated. It was shown that lectins could be used to distinguish the two major series of chromogranins from each other, from dopamine beta-hydroxylase and from several minor, unidentified glycoprotein components of the lysate. Antibody decoration revealed a complex series of peptides containing enkephalin sequences, some of which changed their electrophoretic mobility on treatment with trifluoromethanesulphonic acid.

Adrenal Medulla↗

Parasites, diseases, and health status of sympatric populations of fallow deer and white-tailed deer in Kentucky.

In August 1983, a study on parasites, diseases, and health status was conducted on sympatric populations of fallow deer (Dama dama) and white-tailed deer (Odocoileus virginianus) from Land Between The Lakes, Lyon and Trigg counties, Kentucky. Five adult deer of each species were studied. White-tailed deer had antibodies to epizootic hemorrhagic disease (EHD) virus and Leptospira interogans serovariety icterohemorrhagiae, and fallow deer had antibodies to bluetongue and EHD viruses. Serologic tests for bovine virus diarrhea virus, infectious bovine rhinotracheitis virus, parainfluenza3 virus, and Brucella spp. were negative. One white-tailed deer had an infectious cutaneous fibroma, and one fallow deer had pulmonary mucormycosis. White-tailed deer harbored 16 species of parasites, all of which are considered typical of the parasite fauna of this host in the southeastern United States. Fallow deer harbored nine species of parasites, including eight species known to occur in white-tailed deer on the area and one species (Spiculopteragia assymmetrica) that is not. All fallow deer had inflammatory lesions in the spinal cord and/or brain that were attributed to prior infection with meningeal worm (Parelaphostrongylus tenuis), indicating that P. tenuis infections are not always fatal for this species. The apparent high rate of exposure of Land Between The Lakes fallow deer to P. tenuis without a resultant high rate of clinical cerebrospinal parelaphostrongylosis is hypothesized to be due to a low prevalence and intensity of P. tenuis, partial innate resistance of fallow deer, and acquired immunity.

Animals↗

Recombinant interleukin 2 enhanced natural killer cell-mediated cytotoxicity in human lymphocyte subpopulations expressing the Leu 7 and Leu 11 antigens.

Highly purified recombinant human interleukin 2 (rIL 2) markedly augments the natural killer (NK) cell-mediated cytotoxicity of peripheral blood lymphocytes. In this study, we examined the cellular and metabolic basis of rIL 2-mediated activation of human lymphocyte subpopulations expressing the NK cell-associated surface antigens Leu 7 and Leu 11. All rIL 2-responsive cytotoxic NK cells were found within the subset of lymphocytes expressing the Leu 11 marker, an antigen associated with the Fc-IgG receptor on human NK cells. Cells lacking the Leu 11 antigen, including cells expressing another NK cell-associated marker, Leu 7, did not express NK cell-mediated cytotoxicity either before or after rIL 2 treatment. By contrast, rIL 2 augmented the NK activity of both Leu7-,11+ and Leu 7+,11+ subpopulations. Activation of Leu 11+ NK cells resulted from a direct effect of rIL 2 on these cells and neither required nor was amplified by the presence of T lymphocytes. Enhanced NK cell-mediated cytotoxicity occurred within 4 hr after exposure to rIL 2, and was blocked by the protein synthesis inhibitor cyclohexamide, but not by the DNA synthesis inhibitor mitomycin C or 1500 rad of x-irradiation. Neither Tac antigen, a high-affinity receptor for IL 2, nor other activation markers, such as transferrin receptor or HLA-DR antigen, were detectable on a significant proportion of Leu 11+ cells, either before or after incubation with rIL 2 for 48 hr. In addition, saturating concentrations of antibodies to each of these markers had no effect on the enhancement of NK activity by rIL 2. Finally, preliminary experiments with neutralizing antibodies to gamma- and alpha-interferons also failed to prevent rIL 2 enhancement of NK cell-mediated cytotoxicity, suggesting that rIL 2 does not mediate its effect via release of these cytokines.

Antibodies, Monoclonal↗

Natural killer cells activated in a human mixed lymphocyte response culture identified by expression of Leu-11 and class II histocompatibility antigens.

Lymphoid cells with natural killer (NK)-like function, morphology, and antigenic phenotype have been identified in a mixed lymphocyte culture generated by co-culture of human peripheral blood mononuclear cells with an allogeneic human B lymphoblastoid cell line CCRF-SB. The majority of these mixed lymphocyte (MLR)-response activated NK cells express the Leu-11 surface antigen, but do not express certain T cell-associated antigens (Leu-1, Leu-3, and Leu-4) or the mature monocyte specific antigen, Leu-M3. Unlike most freshly isolated Leu-11+ human NK cells, the MLR-activated Leu-11+ cells expressed class II major histocompatibility antigens, DR and DC. Concomitant with expression of class II gene products, the Leu-11+,DR+ NK cells demonstrate enhanced cytotoxicity against the NK-sensitive tumor cell line K562. The presence of mitotic cells in the Leu-11+,DR+ population and the acquisition of increased levels of transferrin receptor on the cell surface were further indicators of activation of these cells. The direct precursors of the MLR-activated Leu-11+,DR+ cell were Leu-11+ cells that lacked expression of another NK-associated antigen Leu-7, i.e., Leu-7-,11+. These studies provided a definitive identification of the "NK-like" cell in MLR cultures and thus allow quantitation and isolation of these cells for further study.

Cell Line↗

A human natural killer cell-associated antigen defined by monoclonal antibody anti-Leu (NKP-15): functional and two-color flow cytometry analysis.

A monoclonal antibody, anti-Leu 11a (NPK-15), was generated against human large granular lymphocytes (LGL). Anti-Leu 11a reacted with the majority of Percoll gradient-enriched LGL cells, a subpopulation of peripheral blood lymphocytes (PBL) approx (approximately 10-20%), and most granulocytes, but not with a significant number of monocytes, T lymphocytes, or erythrocytes. Cell sorting experiments demonstrated that the Leu 11a+ population encompassed essentially all functional natural killer (NK) cells in the peripheral blood. Two-color flow cytometry analysis of PBL populations stained with anti-Leu 11a and anti-Leu 7 revealed the existence of four distinct populations: Leu 11a-, 7+; Leu 11a+, 7-; Leu 11a+, 7+; and Leu 11a-, 7-. The Leu 11a+ population did not appear to include cells marked with the T cell-associated antigens Leu 1, Leu 2, or Leu 3. The existence of a cell surface antigen common to granulocytes and NK cells, which is capable of distinguishing subpopulations of Leu 7+ cells, provides a useful probe to analyze the nature of the NK lineage.

Antibodies, Monoclonal↗

Characterization and expression of the HLA-DC antigens defined by anti-Leu 10.

The expression of HLA-DC antigens on peripheral blood mononuclear cells, in tonsil and lymph node tissue sections, on tumor cell lines, and on activated T cells was studied using monoclonal antibody, anti-Leu 10. Anti-Leu 10 reacts with HLA-DC molecules on homozygous B cell lines expressing HLA-DR 1,2,4,5,6,8, and 9. It reacts with heterozygous B lymphocytes expressing DR7 and DRw10, suggesting it also recognizes HLA-DC molecules linked to DRw10. The HLA-DC molecules detected by anti-Leu 10 are expressed on all Ig-positive and DR-positive peripheral B lymphocytes and an apparent subpopulation of DR-positive peripheral blood monocytes. Two-color immunofluorescence experiments using phycoerythrin-anti-HLA-DR (L243) and FITC-anti-Leu 10 demonstrated a correlation of the amounts of HLA-DR and DC antigens expressed on B lymphocytes. Cells expressing relatively low, or high amounts of one Class II molecule express respectively low or high amounts of the other Class II molecule. Anti-Leu 10 reacted with all B lymphocyte derived tumor cell lines not with lines of myeloid or erythroid origin, and with only one T cell derived line, HUT-78 which has an activated T cell phenotype. Consistent with this result, anti-Leu 10 binding suggested the presence of HLA-DC on activated T cells in lymphoid tissue, in addition to staining B cells. HLA-DC was also detected on mitogen and MLC activated T cells by anti-Leu 10 binding. Anti-Leu 10 is, therefore, a useful reagent for further studies of the role of HLA-DC in T cell activation and in normal B cell and monocyte functions.

Antibodies, Monoclonal↗

Catheter-induced coronary artery spasm: an angiographic manifestation of vasospastic angina?

During a 4-year period, 33 patients with angiographic coronary artery spasm in the absence of significant fixed occlusive disease were reviewed. Sixteen patients had typical variant angina and 17 had catheter-induced spasm. All patients had one or more episodes of rest angina. Left ventriculography demonstrated mitral valve prolapse in 14 patients (42%) and end-systolic cavity obliteration in six (18%). Spasm was demonstrated to occur in the right coronary artery in 26 patients and in the left coronary artery in seven. Two patients had multivessel spasm. Comparing patients with variant angina and catheter-induced spasm demonstrated no significant difference in clinical, ECG, or angiographic parameters. Two patients with catheter-induced spasm had healed myocardial infarctions and both developed spontaneous non catheter-induced spasm in the infarct vessel. The majority of patients responded to long-acting nitrate therapy, though those with catheter-induced spasm tended to have more recurrent chest pain. Six patients were placed on calcium antagonist drugs with marked symptomatic improvement in five. This study suggests that patients with catheter-induced spasm are similar to those with variant angina and its angiographic documentation may be a marker for the identification of patients with vasospastic angina.

Adult↗