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Biomedical subjects

K Guy

Publications and source records attributed to K Guy.

At least 19 recordsLinked to original sources
PubMed2001

Aluminium lactate treatment of DQ12 quartz inhibits its ability to cause inflammation, chemokine expression, and nuclear factor-kappaB activation.

In 1997, an IARC Working Group classified quartz (crystalline silica) as a Group 1 lung carcinogen, but only in some industries, i.e., the quartz hazard is a variable entity. The reactivity of the quartz surface may underlie its ability to cause inflammation, and treatments that ameliorate this reactivity will reduce the quartz hazard. In this study we treated quartz (Q) with aluminium lactate (AL), a procedure that is reported to decrease the quartz hazard, and explored the effect this had on the highly reactive quartz surface and on proinflammatory events in rat lungs. Aluminium lactate-treated quartz showed a reduced surface reactivity as measured by electron spin resonance and the hemolysis assay. Eighteen hours after instillation of Q into the rat lung, there was massive inflammation as indicated by the number of neutrophils in the bronchoalveolar lavage (BAL). In addition, Q induced an increase in BAL macrophage inflammatory protein-2 (MIP-2) while ALQ had no significant effect compared to control. Epithelial damage, as indicated by BAL protein and gamma glutamyl transpeptidase, also increased with Q but not with ALQ. Furthermore, Q induced an increase in MIP-2 mRNA by BAL cells while ALQ had no effect compared to controls. There was an increase in nuclear binding of the transcription nuclear factor kappaB (NF-kappaB) in the Q-exposed BAL cells and again no effect on nuclear NF-kappaB binding in BAL cells from ALQ-exposed rats. In conclusion, treatment of the quartz surface with aluminium lactate reduced the reactivity of the particles both in terms of hydroxyl radical generation and in terms of the induction of molecular signaling events leading to inflammation.

Aluminum Compounds↗
PubMed2000

Persistent depletion of I kappa B alpha and interleukin-8 expression in human pulmonary epithelial cells exposed to quartz particles.

Chronic inflammation and fibrosis following quartz inhalation has been associated with persistent up-regulation of several "pro-inflammatory" genes, which are commonly regulated by nuclear factor kappa-B (NF-kappaB). Transcription of the NF-kappaB-inhibitor IkappaBalpha is also under NF-kappaB control, and its de novo synthesis is considered to comprise a negative feedback loop in transient inflammation. To investigate this mechanism in particle inflammation, we have studied IkappaBalpha degradation in A549 cells exposed to DQ12-quartz or TiO(2), in relation to the expression of IL-8. Although both quartz and TiO(2) were found to cause IkappaBalpha degradation, only quartz elicited a mild IkappaBalpha depletion, first appearing at 4 h. TiO(2) was found to cause a higher short-term increase in IkappaBalpha mRNA-expression compared to quartz, whereas the early enhancement of IL-8 expression and release was similar for both particles. Up-regulation of IL-8 expression was found to persist with quartz only. Cotreatment with PDTC and curcumin reduced particle-elicited IL-8 response, whereas cycloheximide caused enhancement of IL-8 mRNA expression in both the quartz- and TiO(2)-treated cells. Our results demonstrate that mineral dusts cause IkappaBalpha degradation, a transient increase in de novo synthesis of IkappaBalpha, and enhanced IL-8 expression in human pulmonary epithelial cells. While IkappaBalpha degradation and early IL-8 expression seem to be general particle phenomena, particle-specific characteristics impact on activation of IkappaBalpha gene transcription, apparently accounting for the different proinflammatory IL-8 responses seen with quartz and TiO(2) in the longer term. These observations may provide an explanation for the transient versus the persistent pulmonary inflammatory status and subsequent differences in pathogenic potency of TiO(2) and quartz.

Blotting, Western↗
PubMed2000

Rapid naming deficits in children and adolescents with reading disabilities and attention deficit hyperactivity disorder.

Seventy-one children in three groups (reading disabilities, ADHD without reading disabilities, and normal controls) were compared on their ability to rapidly name colors, letters, numbers, and objects (RAN Tasks) and alternating letters/numbers and letters/numbers/colors (RAS tasks). Children with reading disabilities were found to be slower on letter- and number-naming tasks and made more errors on all tasks than controls or children with ADHD. There was an age effect for the RAN/RAS tasks, with younger children with reading disabilities performing more poorly on all tasks, while the older children with reading disabilities showed poorer performance only on the letter- and number-naming tasks.

Adolescent↗
PubMed1998

Prostaglandin and fatty acid modulation of Escherichia coli O157 phagocytosis by human monocytic cells.

Phagocytosis by human monocytes is an important primary survival mechanism particularly during bacterial infection. However, the processes that control the events and mediators involved in the activation of monocytes and their impact on the phagocytosis of bacteria are poorly understood. The effect of bacterial endotoxin, interleukin-1 beta (IL-1 beta), fatty acids and prostaglandin E2 (PGE2) on the phagocytosis of fluoroscein isothiocyanate (FITC)-labelled Escherichia coli (O157) by human blood monocytes and U937 cells was studied by flow cytometry. Endotoxin increased the phagocytosis of labelled bacteria by both monocytes and U937 cells. IL-1 beta and the polyunsaturated fatty acids; dihomo-gamma-linolenic and arachidonic acids also increased the phagocytic activity of both monocytes and U937 cells. In contrast, PGE2 suppressed phagocytosis in a concentration-dependent manner. The cyclo-oxygenase inhibitor, ketoprofen, further enhanced the increased phagocytic activity in the presence of endotoxin and interleukin-1 (IL-1) indicating suppression by endogenous prostaglandins. This was confirmed by the data which showed that lipopolysaccharide (LPS) and IL-1 increased PGE2 release and ketoprofen inhibited release. Endotoxin and fatty acids increased IL-1 beta release also, whereas PGE2 inhibited release. The data suggest that phagocytic activity may be linked to changes in IL-1 levels. The data presented in this study also suggest that monocyte phagocytosis in the course of bacterial infection would be altered during pathophysiological events which result in elevation of extracellular fatty acids.

Cell Culture Techniques↗
PubMed1992

Insertion of SMRV-H viral DNA at the c-myc gene locus of a BL cell line and presence in established cell lines.

Mutation of the c-myc gene locus has occurred during in vitro culture of the Burkitt lymphoma cell line Namalwa. Gene cloning and sequencing of this c-myc gene locus has revealed the insertion of incomplete copies of the Squirrel Monkey Retrovirus-Human (SMRV-H) proviral genome. Insertions of the SMRV-H genome were seen in all Namalwa cell lines tested, with multiple insertions being seen in some sublines. Viral particles with the morphology of type-D retrovirus, budding from these cells, were seen by transmission EM. New insertions of the genome were produced spontaneously in these cells. The origins of the type-D retrovirus and its implications for workers in the field are discussed.

Base Sequence↗
PubMed1992

The influence of the In(Lu) gene on expression of CDw75 antigens on human red blood cells.

The influence of the In(Lu) gene on human red blood cell (RBC) expression of CDw75 antigens was examined. CDw75 antigens were increased in expression on Lu(a-b-) cells of the dominant inhibitor type in comparison with red cells from donors of other Lutheran (Lu) phenotypes. In contrast, CD44 epitopes detected with F10-44-2, A3D8 and BU52 monoclonal antibodies (mAb) were decreased in expression on Lu(a-b-) red cells. Among normal blood donors of the common phenotype Lu(a-b+) there was a wide range of expression of CDw75 antigens on red cells. The results show that CDw75 is a quantitative polymorphism of human red cells and, among antigens influenced by the In(Lu) gene, is unique in being up-regulated in expression.

Antigens, CD↗
PubMed1991

Burkitt lymphoma cell lines are prone to recombination in the switch region of the Ig mu heavy chain locus.

Different recombinations have been found at the Ig heavy chain gene loci in a number of sublines of the Burkitt lymphoma (BL) cell line Namalwa, following prolonged in vitro culture. The Namalwa sublines examined are DNA fingerprint-identical and derived from a monoclonal source. Recombinant DNA clones were used to map the Ig heavy chain gene mutations to a region between the VDJ and C mu segment of the locus. This region is associated with Ig heavy chain class switching in normal B cells. Of 24 clones established from one subline, three were found to have additional VDJ-C mu region mutations, indicating a high frequency of mutation at this locus.

B-Lymphocytes↗
PubMed1991

Expression of the CDw75 (beta-galactoside alpha 2,6-sialyltransferase) antigen on normal blood cells and in B-cell chronic lymphocytic leukaemia.

Using monoclonal antibodies (mAb) characterized at the last International Workshop on Human Leucocyte Antigens, we examined the expression of CDw75 antigens (beta-galactoside alpha 2,6-sialyltransferase) on normal peripheral blood cells and on cells from patients with B-cell chronic lymphocytic leukaemia (CLL). The mAb used (HH2, EBU.65, EBU.141 and OKB4) detect different epitopes of CDw75. Normal peripheral blood B cells expressed high levels of CDw75 detectable with HH2, EBU.65 and EBU.141 but did not react with OKB4. Cells from patients with B-cell CLL closely resembled normal B cells. All CDw75 epitopes, including OKB4, were strongly expressed on some Namalwa variant Burkitt lymphoma cell lines. The OKB4 epitope was also present on red cells from all normal donors. The other CDw75 mAb were unreactive with red cells from some normal donors. The CDw75 epitope detected with EBU.65 was present on most CD4+ T cells and on a minority of CD8+ cells. HH2 and EBU.141 stained only small numbers of T lymphocytes. OKB4 did not react with T cells. EBU.65+, CD4+ T cells had low levels of expression of CD45R0, CD29, CD54 and CD58, and had high levels of CD45RA antigen. Phytohaemagglutinin (PHA) activation of cells led to the loss of EBU.65 binding. These results suggest that the CDw75 epitope recognized by the EBU.65 mAb is a marker of native T lymphocytes. On B CLL cells the epitopes detected with HH2, EBU.65 and EBU.141 were destroyed by treatment with neuraminidase. Treatment of B-CLL cells and red cells with neuraminidase increased the binding of OKB4, suggesting that this epitope is masked by sialic acid. The results suggest that CDw75 is a sialylated cell-surface antigen expressed in a number of tissue-specific isoforms.

Antigens, CD↗
PubMed1990

Recurrent mutation of immunoglobulin and c-myc genes and differential expression of cell surface antigens occur in variant cell lines derived from a Burkitt lymphoma.

The phenotypic and molecular genetic characteristics of 4 variant sublines of the Burkitt lymphoma cell line Namalwa have been examined. The sublines are DNA-fingerprint-identical and derived from a monoclonal tumour, as shown by a rearrangement of the T-cell-receptor beta-chain gene common to the 4 sublines. There is non-co-ordinate expression of MHC class-I MHC class-II, surface immunoglobulin and a number of antigens recognized by CD MAbs on the different sublines. These different phenotypes of the cells are reminiscent of B cells arrested in varying states of cellular maturity. On Southern blots there are different patterns of restriction fragments hybridizing with Ig heavy- and light-chain gene probes among the sublines, indicating that multiple rearrangements or mutations of Ig genes have occurred in the cells. Different patterns of hybridizing fragments among the sublines were also found by using c-myc probes, implying the existence of different mutations of the c-myc locus. The c-myc mutation found in one of the sublines mapped to the 5' flanking sequence and in another 3' to the c-myc locus. Using the J17BS8 probe, which detects a restriction fragment length polymorphism in the 3' flanking region of the c-myc gene, a 4-fold variation in the gene copy number among the subline was found and one of the sublines was shown to be hemizygous for c-myc. Examination of DNA from early cultures of Namalwa cells showed that the alternations in Ig and c-myc structure had occurred on prolonged culture of the cells.

Antibodies, Monoclonal↗
PubMed1990

Establishment of a karyotypically normal B-chronic lymphocytic leukemia cell line; evidence of leukemic origin by immunoglobulin gene rearrangement.

A new Epstein-Barr virus (EBV) transformed cell line was established from a patient with B-chronic lymphocytic leukemia (B-CLL). The karyotype of the cell line has remained normal for over 12 months in culture; however, identical heavy and light chain immunoglobulin (Ig) gene rearrangements in the patient's blood and the cell line provided evidence that the EBV transformed cells were derived from the neoplastic clone.

Aged↗
PubMed1988

Indirect immunofluorescence labelling with complexes of phycoerythrin and monoclonal anti-phycoerythrin antibodies (PEAPE complexes).

We describe a method of immunofluorescence which is a lateral application of the principles of the APAAP immunohistochemical technique. Immune complexes of R-phycoerythrin and monoclonal anti-R-phycoerythrin (PEAPE complexes) were used in an indirect immunofluorescence technique to detect the binding to cells of monoclonal antibodies directed to IgM, HLA-DR and B cell activation and differentiation antigens. PEAPE complexes were linked to cell surface bound mAbs by unlabelled anti-mouse Ig antibodies to produce high levels of fluorescent staining. The sensitivity of this method of indirect immunofluorescence was enhanced by the sequential application of several cycles of anti-mouse Ig and PEAPE complexes.

Animals↗
PubMed1987

Immunology in diabetic pregnancy: activated T cells in diabetic mothers and neonates.

Lymphocytes bearing surface antigens indicating early and full activation have been evaluated, in addition to T cell subsets, in blood samples from diabetic pregnant patients, neonates from diabetic mothers and control groups. The type of diabetes and the trimester of pregnancy were taken into account. Monoclonal antibodies were used to enumerate total T cells, helper/inducer, cytotoxic/suppressor Tlymphocytes and activated mononuclear cells using antibodies binding lymphocyte surface antigens as markers of early lymphocyte activation, and MHC Class II surface antigens as markers of late activation. A decrease in T-helper cells during the third trimester of pregnancy in Type 1 (insulin-dependent) and gestational diabetic patients (p less than 0.02) and a decrease in T-suppressor cells in Type 2 (non-insulin-dependent) diabetic pregnant patients during the third trimester (p less than 0.01) were observed in relation to normal values. As in normal pregnancy, 4F2-positive cells were increased in 48% of diabetic pregnant patients during the second and third trimesters of gestation. Class II-positive cells were increased in almost 60% of Type 1 and gestational diabetic patients during the last trimester of pregnancy in comparison with normal pregnant women and control subjects. A decrease in T-helper cells (p less than 0.02) and a clear increase in 4F2-positive cells (p less than 0.001) and Class II-positive lymphocytes (p less than 0.005) were observed in the infants of diabetic mothers in comparison with control subjects. The maternal cellular immune system, actively altered in pregnancy, is fully activated in a number of Type 1 and gestational diabetic pregnant patients. Activated lymphocytes are even found in the neonates of diabetic mothers, but these do not trigger the events leading to the onset of diabetes in the short term.

Adult↗
PubMed1987

Keratinocyte expression of MHC class II antigens in allergic sensitization and challenge reactions and in irritant contact dermatitis.

Keratinocytes expressed major histocompatibility complex class II antigens during the development of irritant contact dermatitis, and during the induction of contact hypersensitivity, as well as in established allergic contact dermatitis. A battery of anti-class II monoclonal antibodies, some of which are specific for class II subregion products (DP, DQ, DR), was used in an immunohistochemical study of the sequential changes in the allergic challenge reactions to dinitrochlorobenzene (DNCB) and nickel, the irritant response to anthralin, and the induction of sensitization to DNCB. The induction of keratinocyte class II expression paralleled the influx of Leu-3a+ T cells into the skin and had occurred by 24 or 48 h in each type of reaction. Differential expression of class II subregion products on keratinocytes was noted: DR was the most frequently expressed molecule, followed by DP and DQ, although in the irritant response, DP expression was not observed. The importance of these observations can be decided only by functional studies.

Anthralin↗
PubMed1987

T-24.B-cell differentiation factor induces immunoglobulin secretion in human B cells without prior cell replication.

Stimulation of B lymphocytes from B-cell chronic lymphocytic leukaemia (B-CLL) with 12-0-tetradecanoylphorbol-13-acetate (TPA) has shown that these cells are capable of differentiation (Totterman, Nilsson & Sundstrom, 1980). Increases in the expression of different class II MHC antigens (Guy et al., 1983, 1986) and responsiveness to growth factors (Kabelitz et al., 1985; Suzuki, Butler & Cooper, 1985) have been studied. Supernatant from the human bladder carcinoma line T-24 contains a B-cell differentiation factor (BCDF) able to induce immunoglobulin secretion from CESS cells. We investigated the induction of proliferation and immunoglobulin secretion in human B cells by studying the effects of this factor on B-CLL cells, in both the presence and absence of TPA. We report here that this material (termed T-24.BCDF) causes immunoglobulin secretion to be initiated in these cells, and that this is not accompanied by detectable DNA synthesis. These observations were extended to normal human B cells and demonstrate that human B cells can secrete immunoglobulin in the absence of clonal expansion.

B-Lymphocytes↗
PubMed1987

Variant sublines of the human B-lymphoma cells Namalwa are at different stages of differentiation.

Variant sublines of the Burkitt's lymphoma cell line Namalwa, previously shown to differ in MHC class II antigen and immunoglobulin expression, have been tested with monoclonal antibodies defining B-cell specific clusters of differentiation (CD). The Namalwa sublines express antigens recognized by the CD antibodies in patterns that indicate that the cells are arrested at different stages of differentiation.

Antigens, Neoplasm↗
PubMed1986

Activated T cells in normal pregnant women and neonates.

The phenotyping of T-cell subsets and T cells at different stages of activation was performed using a panel of monoclonal antibodies in samples from normal pregnant women at different stages of gestation and in the cord blood of neonates. The data obtained from pregnant women showed a slight decrease in the total number of T cells at the beginning of pregnancy, whereas there was a clear increase in 4F2-positive lymphocytes after a few months of gestation. No significant increase in Class II-positive lymphocytes was observed in normal pregnant women in comparison with adult healthy women. The data from neonates revealed a clear decrease of OKT3- and OKT4-positive cells and an increase of 4F2-positive cells in comparison with control subjects. These data indicate that alerted, but not fully activated, lymphocytes are present in the circulation of both the mother, after the first months of pregnancy, and the neonate. This finding reinforces the concept that during pregnancy there is an activation of certain immune components rather than a general depression of the immune system.

Adult↗