Search PubMed⌕ Search

Biomedical subjects

D Engel

Publications and source records attributed to D Engel.

At least 55 records · Page 3Linked to original sources
PubMed1986

T-cell differentiation antigens and antigenic lymphocyte reactivity in pleural effusions.

Blood and pleural effusion mononuclear cells from thirteen patients were examined for the expression of T lymphocyte differentiation antigens as well as in vitro thymidine incorporation. The ratio of T4 to T8 cells was significantly greater among pleural effusion lymphocytes than among blood lymphocytes. Effusion lymphocyte responses to phytohaemagglutinin were less than those of blood lymphocytes. Unstimulated thymidine incorporation was greater in pleural effusion lymphocytes. Antigen-stimulated lymphocyte reactivity was not consistently greater in either blood or effusion lymphocytes. Lymphocytes from tuberculous effusions all reacted to tuberculin. Pleural effusion lymphocytes, regardless of the etiology of the effusion, possessed the same range of antigenic specificities as did blood lymphocytes. Therefore, effusion lymphocyte responsiveness to tuberculin does not prove the presence of tuberculous pleurisy but does indicate sensitisation to tuberculin.

Adult↗
PubMed1985

Genetic control of mitogen-induced B-cell hyperproliferation in SM/J mice.

Previous studies have shown that B cells from SM/J mice exhibit hyperproliferative responsiveness to several bacterial-derived B-cell mitogens. This hyperresponse trait was found to be under autosomal, polygenic control by non-H-2 genes. We have now estimated the number of genes involved by statistical analysis of the proliferative responses of splenocytes from SM/J and low-responder C57BL/6J strains, and progeny from the (B6 X SM)F1, F2 and (F1 X B6) crosses. The number of loci involved was ascertained using two different statistical approaches. An estimate of two loci was determined using chi-squared statistics. The second approach, based on an additive model in the natural log scale, also pointed to a lower bound of two genes. We conclude that the hyperresponse to B-cell mitogens in SM/J mice is determined by two autosomal genes which are not linked to the H-2 major histocompatibility complex.

Animals↗
PubMed1985

Immunoregulation in severe generalized periodontitis.

Severe generalized periodontitis (SGP) is an inflammatory disease which leads to extensive alveolar bone loss in young adults. Peripheral blood lymphocytes from SGP patients have been previously reported to exhibit an in vitro hyperproliferative response when exposed to B cell mitogens derived from Staphylococcus aureus and Actinomyces viscosus. Therefore hyperresponsiveness to B-cell mitogens could be an important pathogenic factor in the susceptibility to and progression of SGP. We have tested whether the hyperproliferative response of lymphocytes from SGP patients was due to (i) a functional deficiency of suppressor T cells, or (ii) to numerical alterations of lymphocytes. Supernatant fluids from concanavalin A-stimulated T cells from 14 SGP patients and 14 normal subjects were compared for their ability to suppress the IgM synthesis of B-cell mitogen-stimulated mouse splenocytes. No significant differences were noted in suppressor T-cell function between control subjects and SGP patients. However, SGP patients had significantly higher lymphocyte counts than control subjects, and there was a positive correlation between high lymphocyte counts and high mitogen-stimulated proliferation. SGP patients also had higher lymphocyte:monocyte ratios than control subjects, suggesting that a defect in macrophage-mediated suppression might be involved in the hyperproliferation phenomenon. Our data do not support the hypothesis that a suppressor T-cell defect is the cause of mitogen-induced hyperproliferative responsiveness of peripheral blood lymphocytes from SGP patients. Rather, hyperproliferation may be due to an expansion of the lymphocyte pool which responds to mitogens, or/and a regulatory disturbance which arises because of altered lymphocyte:macrophage ratios.

Actinomyces↗
PubMed1984

Conformational alterations of transcription termination protein rho induced by ATP and by RNA.

Transcription termination protein rho from Escherichia coli possesses an RNA-dependent ATP hydrolysis activity necessary for expression of its termination function. We have used the rate of trypsin-mediated inactivation of ATPase activity as a conformational probe to test for ligand binding-induced conformational changes in the rho polypeptide. When present in molar excess over rho polypeptide, trypsin inactivates rho ATPase by a first order process that correlates well with the loss of intact rho polypeptide. When rho protein binds poly(C) or poly(dC), its susceptible bonds become more accessible to trypsin action. On the other hand, when rho binds either ATP or ADP those bonds become less accessible. These results suggest that rho protein assumes an altered conformation when an RNA cofactor is bound and that is assumes a distinctly different conformation when a nucleotide substrate or product is bound. A special change in the accessibility of trypsin-susceptible bonds is also detected when rho in its complex with poly(C) is catalyzing the hydrolysis of ATP.

Adenosine Triphosphatases↗
PubMed1984

Mitogen-induced hyperproliferation response of peripheral blood mononuclear cells from patients with severe generalized periodontitis: lack of correlation with proportions of T cells and T-cell subsets.

Severe generalized periodontitis (SGP) is a localized inflammatory disease which differs clinically from common periodontitis in that it leads to remarkable extensive alveolar bone loss in relatively young adults. There is evidence that B-cell responses to bacterial substances may play a major role in the pathogenesis of this disease. In the present report, we show that a B-cell mitogen from Actinomyces viscosus (AVIS) bacteria provokes a hyperproliferation response of peripheral blood mononuclear cells (PBMNC) from these patients. In addition, AVIS-stimulated PBMNC from SGP patients proliferate for longer periods in culture than do PBMNC from control subjects. There were, however, no differences between patients and controls in the numbers of immunoglobulin-secreting cells in these cultures as determined by an indirect plaque-forming cell assay. The possibility that differences in numerical proportions of regulatory T-cell subsets may play a role in the mitogen-induced hyperproliferation phenomenon is examined. PBMNC were stained with fluorescein isothiocyanate-conjugated monoclonal antibodies OKT3, OKT4, and OKT8 in order to identify, respectively, total T cells, helper/inducer, and suppressor/cytotoxic subsets. Flow cytometric analysis of such specifically stained cell preparations from 14 control subjects and 14 SGP patients did not reveal any significant differences between the proportions of total T cells or T-cell subsets of the two groups. Furthermore, there were no statistically significant correlations between the magnitude of proliferation responses and the proportions of total T cells or either of the T-cell subsets.

Adult↗
PubMed1983

Amplification and organization of dihydrofolate reductase genes in a human leukemic cell line, K-562, resistant to methotrexate.

A subline of human leukemia cells (K-562), highly resistant to methotrexate, was developed by stepwise selection in the presence of increasing concentrations of this drug. The ED50 of these resistant cells was 1 mM compared to 10 nM for the parental line. Comparison of certain folate-requiring enzymes from crude extracts of the parent and resistant cells showed a 240-fold elevation of dihydrofolate reductase activity in the resistant cells with no significant increase in the levels of the other enzymes. Purified dihydrofolate reductase from the resistant cells had the same physical and kinetic properties as the enzyme from the sensitive cells. Southern blot analysis showed a marked increase in the number of dihydrofolate reductase genes in the resistant line. The genomic organization of the human dihydrofolate reductase gene was determined by hybridization with specific cDNA sequences from a human cDNA to DNA fragments from K-562 cells generated by restriction endonucleases. The human dihydrofolate reductase gene contained at least four intervening sequences and was approximately 30 kb in size. Northern blot studies demonstrated an increase of dihydrofolate reductase mRNA species; the predominant message was 3.8 kb. Karyotype analysis revealed three elongated marker chromosomes, derived from chromosomes 5, 6, and 19 which contained homogeneous staining regions, which were not present in the parent cell line.

Cell Line↗
PubMed1983

Heartburn treated with tapwater.

A very simple and effective method against heartburn (Hb) is described; it consists in drinking 1-2 glasses of tapwater. A larger scale trial of the method is also recommended against heartburn during the first trimester of pregnancy and possibly against peptic ulcer.

Drinking↗
PubMed1983

Accelerated rate of mononuclear phagocyte production in vitro by splenocytes from autoimmune motheaten mice.

The rapidly fatal autoimmune disease accompanied by pneumonitis in the mutant mouse known as motheaten is caused by an autosomal recessive gene. The proliferative capacity and production rate of splenic mononuclear phagocytes at different maturational stages, defined by morphologic criteria, were examined by two in vitro tritiated thymidine administration protocols and radioautography. The replicative rate of splenic promonocytes from 3-week-old normal mice was found to approximate that of adult bone marrow cells. Monocytes, macrophages, and previously described macrophagelike cells from motheaten mice had an accelerated rate of maturation in vitro, compared with similar cells from normal mice. These differences in the production rates could be attributed to the shorter period of time that promonocytes from the mutant mice are in the S phase of the cell cycle. Evidence, also, verified that the macrophagelike cells were derived from promonocytes via the monocyte-macrophage compartment. The unusual in vitro growth characteristics of the splenic mononuclear phagocytes from motheaten mice could be a manifestation of an in vivo abnormality of this lineage that could contribute to the development of pulmonary disease in these animals.

Animals↗
PubMed1982

The effects of immunosuppressive drugs on periodontal inflammation in human renal allograft patients.

The periodontal status of four kidney allograft patients was determined before and at periodic intervals for 9 months after receipt of the allografts. These patients received immunosuppressive drugs as part of their therapy, beginning at the time of transplantation. Three hemodialysis patients with analogous kidney disease and six eye patients who were otherwise healthy served as controls. Comparisons of plaque levels, pocket depths and gingival inflammation were made between the three groups of subjects. The results suggest that the administration of the immunosuppressive drugs significantly reduces the level of gingival inflammation in the presence of high levels of bacterial plaque. Pocket depths did not change significantly in eigher the allograft or control groups. Whole not conclusive, the findings support the hypothesis that host inflammatory and immunological responsiveness to plaque bacteria is a primary factor in the pathogenesis of destructive periodontal disease in humans.

Adult↗
PubMed1982

Abnormal in vitro proliferation of splenic mononuclear phagocytes from autoimmune motheaten mice.

Motheaten mice develop combined immunodeficiency and fatal autoimmune disease that follow autosomal recessive inheritance. In splenocyte cultures of motheaten mice, supplemented with 5% normal serum proliferating cells (MP) were present exhibiting morphologic characteristics of mononuclear phagocytes at light and electron microscopic levels. The macrophage nature of these cells was confirmed by the lack of Thy-1 antigen and immunoglobulins; the expression of Mac-1 antigen, FcR for IgG, and Ia antigens on their cell surfaces; their ability to phagocytize EA and adhere to plastic; the presence of nonspecific esterase and lysomal enzymes in their cytoplasm; and the pattern of peroxidase localization similar to monocyte-derived macrophages. MP from motheaten mice exponentially grew in culture in the absence of exogenous growth factors with a doubling time of approximately 76 hr. Although these cells were present in splenocyte cultures of normal controls, their number did not increase during the culture period under the same conditions. The addition of dextran sulfate further enhanced the proliferation of MP from motheaten mice, and induced exponential growth of these cells from normal controls, reaching only the level of unstimulated cells from motheaten mice. Radioautographic analysis demonstrated that MP substantially contributed to the elevated spontaneous and dextran sulfate-induced DNA synthesis in splenocyte cultures. Therefore, the in vitro abnormality of MP may be indicative of in vivo aberrancies of macrophages from motheaten mice and lends credence for investigating the role of macrophages in immunodeficiency and autoimmunity that develop very early in motheaten mice.

Animals↗
PubMed1981

Immune responsiveness of SM/J mice. Cellular characteristics and genetic analysis of hyperresponsiveness to B cell mitogens.

We tested the proliferative responses of splenocytes from a panel of inbred mouse strains to AVIS, a B cell mitogen from Actinomyces viscosus bacteria. The SM/J strain was found to exhibit severalfold higher responsiveness than any of the other strains. SM/J splenocytes were also hyperresponsive to the B cell mitogens lipopolysaccharide, dextran sulfate, and purified protein derivative of tuberculin, but responsiveness to the T cell mitogen phytohemagglutinin was normal. (B6 X SM)F1 and F1 x B6 backcross mice were tested for AVIS and lipopolysaccharide responsiveness, and it was determined that hyperresponsiveness was under polygenic, autosomal, non-H-2-linked gene control. Genetic control of response to B mitogens in SM/J mice appears to be expressed solely through the B lymphocyte because removal of T lymphocytes or macrophages did not reduce the magnitude of responsiveness in vitro. SM/J mice may provide a useful model for testing questions regarding B cell triggering, differentiation, and function, and to examine the genes involved with B cell proliferation.

Animals↗
PubMed1981

Elective vital staining of mouse tumors with labelled dyes.

It was shown by vital staining in previous experiments (1) that carcinoma and sarcoma of mice could be selectively stained by certain dyes of the triphenyl methane sulphonic acid group. These findings were now confirmed in the present experiments by using labelled (125I) dyes of the same chemical group. In some mice the tumor tissue was the most radioactive, compared with other tissues. In other mice the tumor tissue was exceeded only by tissues which had a blood supply 5-time to 35-times higher. These were, in addition, excretory organs the excreta of which was highly radioactive (kidney and liver). The urine was 50-times more radioactive than the tumor and the bile was most probably not less. After deduction of the radioactivity of these two components, blood and excreta, from the radioactivity of the parenchyma tissue of the kidney and liver, the tumor tissue proved to be the most radioactive of all tissues tested. This indicates that tumor tissue retained the administered labelled dyes in higher concentration than all other tissues.

Animals↗
PubMed1981

Tropical pyomyositis, a thiamine-deficiency disease.

On the basis of clinical observations made in Shanghai which confirmed the clinical and experimental findings of Osawa in Japan, it is suggested that thiamine deficiency is an essential contributary factor in producing tropical pyomyositis (TPM). It was found that the majority of patients affected by TPM suffer or have previously suffered from beriberi. The practical disappearance of TPM in Japan in recent years supports the above view. Thiamine deficiency induces a biochemical lesion (Peters) in the pyruvate oxidase system of the muscle, which breaks down its normal resistance to infection and opens the gate to bacterial agents. It is possible that in different parts of the world other or additional factors may play a similar role to that of thiamine deficiency. It is suggested that a wide survey should be undertaken--perhaps by the World Health Organisation--especially in areas in which TPM is endemic, using all relevant methods, to elucidate the factor or factors responsible for the development of TPM.

Adult↗
PubMed1981

Immunologic tolerance to collagen and glycosaminoglycan components of scleral allografts in humans. Evidence for T cell suppression.

Unfractionated peripheral blood lymphocytes (PBL) and the T and B cell fractions of PBL from four patients who had received scleral allografts, and fractions from four control subjects were tested in vitro for proliferative responsiveness to collagen and glycosaminoglycan-enriched extracts of allogeneic sclera. None of the unfractionated lymphocyte cultures (patients and controls) were responsive to the scleral extracts. However, B-enriched lymphocyte cultures from one patient and two control subjects did respond to the scleral extracts, although there was considerable individual variation in the magnitudes of these responses (stimulation indices ranging from 1.5 to 11.5). In contrast, the DNA-synthesis response of T cells to scleral extracts was strongly suppressed. Furthermore, T cells pre-exposed for 24 hours to scleral collagen were capable of suppressing B-cell responsiveness to mitogens in autologous mixed lymphocyte cultures. Our findings confirm the lack of apparent adverse immunologic responsiveness to scleral allografts in humans as reported by others. It is possible that immunological tolerance to the scleral allografts is due to a suppressor T-cell mechanism which is triggered by scleral collagen.

B-Lymphocytes↗
PubMed1981

Immune responsiveness of SM/J mice: hyper NK cell activity mediated by NK 1+ Qa 5- cells.

Compared with other inbred strains, SM/J mice have both abnormally high responses to B cell mitogens and hyper NK cell and K cell activity. This hyper NK cell activity is evident even in older SM/J animals, and a high proportion of SM/J nylon-nonadherent lymphocytes that bind target cells also have lytic activity. The SM/J NK cells are NK 1+, Qa 5-, but H-2v identical B10.SM congenic mice have normal NK activity and NK 1+, Qa 5+ NK cells. Together these results suggest the elevation of NK cell activity in SM/J mice is due to chronic activation or maintenance of a Qa 5- NK cell subset. The genetic control of B cell responsiveness and NK cell activity was examined in (B6 x SM)F1 x B6 backcross progeny and (A x SM)F2 intercross mice. No correlation between NK levels and mitogen responsiveness was detected. NK levels in SM/J mice appear to be under polygenic, non-H-2 gene control.

Animals↗