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C D Jennings

Publications and source records attributed to C D Jennings.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effect of human IL-2-activated natural killer and T cells on graft-versus-host disease and graft-versus-leukemia in SCID mice bearing human leukemic cells.

We have previously reported that xenogeneic lethal acute graft-versus-host disease (GVHD) was induced by transplantation of a mixture of human IL-2 activated natural killer (NK) and T cells into SCID mice conditioned with 4 Gy total-body irradiation (TBI), but not by IL-2-activated pure human T cells or NK cells. TBI and transplantation of the mixture of activated cells were both required to produce the lethal effect. We now report the effect of human IL-2 activated NK, T, or NK+T effector cells on the development of acute and chronic GVHD and GVL in SCID mice bearing human leukemic cells. Ten days after being inoculated i.v. with 2 x 10(7) human U-937 or K-562 leukemic cells, SCID mice, hereafter termed hu-leukemic mice, were radiated with 4 Gy TBI and transplanted i.v. with 5 x 10(7) human IL-2-activated NK, T, or NK+T effector cells. Hu-leukemic control mice received neither TBI nor effector cell transplantation. Acute GVHD-positive control SCID mice were transplanted with 5 x 10(7) H-2-incompatible C57Bl/6 splenocytes following 4 Gy TBI. The mice were observed for signs of GVHD and leukemia for 90 days. Twenty of 20 non-effector cell-transplanted control hu-leukemic mice developed signs related to leukemia and died with leukemic infiltration in the brain, liver, kidney, and lung 50-65 days after inoculation. Flow cytometry (FC) demonstrated 21-89% human leukemic cell infiltration in the bone marrow. Fourteen of 14 hu-leukemic mice transplanted with NK+T effector cells did not develop signs of advanced leukemia but died within 17 days of acute GVHD. FC demonstrated no human leukemic cells in their marrow. Twelve of 15 and 18 of 25 hu-leukemic mice transplanted with either NK or T cells survived 90 days without any evidence of symptomatic leukemia (P < 0.01 compared with non-effector cell-transplanted groups). NK-transplanted hu-leukemic animals experienced mild-to-moderate acute GVHD during the first 10-20 days posttransplantation, but gradually recovered and did not develop chronic GVHD. Hu-leukemic animals transplanted with T effector cells manifested no signs of leukemia or acute GVHD but chronic GVHD skin lesions appeared 80-90 days after transplantation. We conclude that acute GVHD, chronic GVHD, and GVL are associated but separable phenomena.

Animals↗
PubMed1995

In vivo reactivity of T cell clones isolated from mice with syngeneic graft-versus-host disease.

Syngeneic graft-versus-host disease (SGVHD) has been shown to occur in murine syngeneic radiation bone marrow chimeras following a short course of cyclosporine. To analyze the effector mechanisms present in diseased animals, four T cell clones (1D5, 1D8, 1C10, 2D8) were isolated from the spleens of C3H/HeN mice late in the disease course by cloning on irradiated syngeneic spleen cells. These clones were CD4+, alpha beta TCR+ and responded to I-Kk in vitro. In addition to I-Ek reactivity, three of the clones exhibited crossreactivity with the superantigen MIs 1a (mtv 7). Clones 1D5 and 1C10 were found to express TCR V beta chains (V beta 4 and V beta 8.1, respectively), which are normally present in the T cell repertoire of C3H/HeN mice. All SGVHD clones were found to be autoreactive in that they responded to syngeneic stimulator cells in the absence of xenogeneic serum proteins. To test in vivo activity, the 1D5 SGVHD clone was injected into the hind footpad of mice where it was shown to induce footpad swelling in a cell dose-dependent, I-Ek-specific manner in sublethally irradiated, but not normal mice. Histological analysis indicated that the clone induced dermal and subcutaneous edema that correlated directly with injection of 1D5 and not the control clone. Preliminary experiments suggested that the other three autoreactive clones behaved in a similar manner. These data are consistent with the involvement of a self-class II-specific CD4+ T cell in murine SGVHD.

Animals↗
PubMed1995

Expression of p53 protein in pancreatic adenocarcinoma. Relationship to cigaret smoking.

We studied the expression of p53 gene product in pancreatic adenocarcinomas of the usual ductal type to determine its relationship to cigarette smoking and its usefulness as an independent prognostic indicator. Twenty-six resection specimens of pancreatic adenocarcinoma were examined by immunohistochemistry using an antigen retrieval solution and monoclonal PAb1801 and polyclonal CM1 antibodies on paraffin-embedded material. Specific nuclear p53 expression for both PAb1801 and CM1 was identified in seven cases (27%). In all cases immunoreaction was confined to neoplastic cells. Three of four (75%) tumors from patients who had never smoked showed immunoreaction, whereas only three of 14 (21%) tumors from smokers showed positive staining. Cases with positive staining had shorter mean survival (6.3 mo) than cases that failed to stain (9.8 mo), but the difference was not statistically significant in this small study. There was no statistically significant association between p53 immunoreactivity and other clinicopathologic parameters. Our findings indicate that abnormalities of p53 gene in pancreatic adenocarcinomas may not be directly related to cigarette smoking. Those patients who survived the longest tended to have tumors negative for p53 immunostaining. p53 immunoreaction may be a useful feature in distinguishing adenocarcinoma from chronic pancreatitis in small biopsies.

Adenocarcinoma↗
PubMed1995

Spontaneous and ionizing radiation induced mutations involve large events when selecting for loss of an autosomal locus.

The mouse P19H22 embryonal carcinoma cell line contains two distinct chromosome 8 homologs, one derived from Mus musculus domesticus (M. domesticus) and the other derived from Mus musculus musculus (M. musculus). It also contains a deletion for the M. musculus aprt allele, which is located on chromosome 8. In this study, cells with spontaneous or induced aprt deficiencies were isolated from P19H22 and examined to determine the nature of the mutational events that had occurred. Ultraviolet radiation (UV), ethyl methanesulfonate (EMS), and two forms of ionizing radiation, 137Cs and 252Cf, were used for mutation induction. DNA preparations from the aprt deficient cells were initially screened with a Southern blot analysis and separated into two broad classes: those that had lost the M. domesticus aprt allele and those that had retained it. The overwhelming majority (> 95%) of the spontaneous and ionizing radiation-induced mutants exhibited aprt gene loss, indicating that relatively large events had occurred and that homozygosity for the deleted region was not a lethal event. Loss of heterozygosity for syntenic markers was found to be a common event in cells exhibiting aprt gene loss. In contrast, a majority of the UV-induced mutants (61%) and a substantial minority of the EMS-induced mutants (38%) retained the aprt gene. A sequence analysis confirmed that base-pair substitutions were responsible for this class of mutation. Gene inactivation associated with hypermethylation of the promoter region was found to be a rare event and was not induced by any of the mutagenic agents tested. The results demonstrate the suitability of the P19H22 cell line for mutational studies, particularly those that are large in nature.

Adenine Phosphoribosyltransferase↗
PubMed1995

Aedes aegypti control in the Lao People's Democratic Republic, with reference to copepods.

An evaluation of the Lao Aedes aegypti control program and of the predatory abilities of copepods from Vientiane, Lao People's Democratic Republic was undertaken before a field release of copepods in Thongkankam village, Vientiane. Copepods were transported to Australia for evaluation of predatory abilities and their survival under various nutrient and pH conditions. Mesocyclops guangxiensis was chosen for release over M. aspericornis due to its higher reproduction rate and its ability to survive in lower nutrient environments. Mesocyclops guangxiensis was released into 142 containers and 20 wells in a village in Vientiane. Copepods were present in 7% of the containers after one month and were absent six months postinoculation. In comparison, 100% of wells were still positive after six months, with average numbers of Ae. aegypti in the wells decreasing from 59.5 +/- 18.5 (+/- SEM) to 0 after six months. Numbers of Culex quinquefasciatus and Anopheles maculatus also decreased to 0 after six months. This study indicates that predacious copepods will be accepted by the community and could be integrated as a low-cost, persistent control agent into new strategies for improving surveillance and control of dengue vectors.

Aedes↗
PubMed1994

Effect of total body irradiation, busulfan-cyclophosphamide, or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2-incompatible transplanted SCID mice.

In a previous study, we found that total body irradiation (TBI) was essential to induce acute graft-versus-host disease (GVHD) after allogeneic H-2-incompatible splenocyte (SP) transplantation in SCID mice. SCID mice (H-2d) conditioned with cyclophosphamide and transplanted intravenously (IV) with 5 x 10(7) C57BL/6 (H-2b) SP developed chronic GVHD within 3 months posttransplant without any evidence of preceding acute GVHD. In this study, SCID mice were conditioned with 4 Gy TBI or non-TBI regimens, either BuCy2 (busulfan 4 mg/kg/d + cyclophosphamide 100 mg/kg/d for 2 days) or Cy5 (cyclophosphamide 100 mg/kg/d for 5 days), and then transplanted IV with 5 x 10(7) SP. The TBI-conditioned mice were further divided into tree transplant groups: (1) TBI and SP administered the same day (TBI + D0 SP), (2) SP administered 4 days post-TBI (TBI + D4 SP), and (3) SP administered 7 days post-TBI (TBI + D7 SP). The severity of GVHD was compared among these groups by clinical and histologic grading. Twenty-eight of 28 mice treated with TBI + D0 SP died of acute GVHD, with overwhelming diarrhea by day 15 posttransplantation. Sixteen mice treated with either TBI + D4 SP or TBI + D7 SP developed acute GVHD, but none of them died of this disorder during 30 days posttransplantation. The mice conditioned with non-TBI regimens developed chronic GVHD within 3 months without showing any detectable signs of acute GVHD. Serum and in situ colonic cytokines were determined by enzyme-linked immunosorbent assay and immunohistology respectively. TBI itself significantly increased both serum and colonic tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and IL-6 when compared with non-TBI regimens and normal controls. TNF-alpha appeared in the serum and colon 4 hours post-TBI and peaked in 24 hours, followed by increasing IL-1 alpha and then IL-6 levels. TNF-alpha and IL-1 alpha decreased rapidly within 3 to 5 days post-TBI if no allogeneic cells were transplanted. Histoincompatible transplantation augmented cytokine release, which remained elevated on day 10 in these animals. Mice treated with TBI + D0 SP developed the most severe acute GVHD and had the highest levels of TNF-alpha, IL-1 alpha, and IL-6. The BuCy2-conditioned mice had the lowest cytokine levels and developed no acute GVHD. When the mice transplanted with TBI + D0 SP were treated immediately with recombinant soluble human TNF receptor (rhuTNFR:Fc) 100 micrograms/d intraperitoneally and for the subsequent 15 days acute GVHD mortality was significantly reduced from 100% to 50% (P < .001).(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1994

Comparative assessment of DNA analysis in effusions by image analysis and flow cytometry.

Cytologic evaluation of body cavity fluids is useful to detect malignancy within the pleural and peritoneal spaces. A definitive diagnosis cannot always be made on cytologic evaluation alone. As malignant processes may show abnormal DNA content, DNA analysis of effusions may be useful. Therefore, we determined the DNA content of 37 effusions by flow cytometry (FC) and image analysis (IA) using the CAS 200. Of the 37 fluids evaluated, 18 were cytologically malignant, 15 benign, and four atypical. Overall, 22 fluids (60%) showed concordance between FC and IA. None of the benign fluids were aneuploid. All showed diploid histograms or diploidy with increased proliferating cells. Three of four atypical fluids had increased proliferating cells by either FC or IA, whereas one was diploid by both methods. Aneuploidy was detected in 13 malignant fluids: five were aneuploid by both methods and eight by only one method. IA identified aneuploidy in five of those eight cases, while three were identified by FC. Three of the cytologically malignant fluids were diploid by both methods, and two showed increased proliferating cells by IA and diploidy by FC. The specificity of both methods was 100%. However, the sensitivity of identifying a malignant fluid by aneuploidy is low, 44% for FC and 55% for IA. IA appears to identify small aneuploid populations more frequently than FC. The detection of aneuploidy in effusions is highly suggestive of malignancy, and the combination of both techniques gives the highest detection rate (72%). However, neither are as sensitive as traditional cytologic evaluation with the occasional use of additional histochemical stains.

DNA, Neoplasm↗
PubMed1994

Proliferating cell nuclear antigen in prostatic adenocarcinoma: correlation with established prognostic indicators.

OBJECTIVE: The utility of an antibody to proliferating cell nuclear antigen (PCNA), a growth-specific nuclear protein, was assessed as a prognostic variable for prostatic adenocarcinoma. Its expression was correlated with established prognostic indicators, including tumor grade, stage, prostatic-specific antigen (PSA), and percent of tumor in the gland at excision. METHODS: Forty archival needle biopsies containing a minimum of four hundred tumor cells were analyzed. Immunoperoxidase staining of paraffin sections was performed for PCNA (PC10) after pretreatment in antigen retrieval solution. A proliferative index (PI) for each case was derived using image analysis with measurement of at least four hundred twenty-five nuclei. RESULTS: PI values ranged from 2.4 to 31.3 percent. Mean PI values varied significantly (ANOVA, p = 0.005) among cases with dominant Gleason grade (DGG) of 3 (mean PI = 9.3%), 4 (mean PI = 13.7%), and 5 (mean PI = 18.8%). By t test, significant differences were noted for PI in cases with DGG 2 and 3 versus those with DGG 4 and 5 (p = 0.0065). PI for cases with DGG 3 versus 5 showed significant difference (p = 0.0017). Tumors of Gleason scores 5 to 7 differed significantly from those with scores 8 to 10 (p = 0.014). A statistical relationship for PI and PSA, clinical stage, and percent tumor at resection could not be established by linear regression. CONCLUSIONS: These findings suggest that additional study of the PI, as determined by PCNA immunohistochemistry and image analysis, may be warranted to determine its usefulness as an adjunctive parameter in prostate adenocarcinoma. This technique may be particularly useful in needle biopsies where limited tumor may render assessment of grade difficult.

Adenocarcinoma↗
PubMed1994

Laboratory studies of desiccation resistance in Mesocyclops (Copepoda: Cyclopoida).

The desiccation resistance of 4 species of Mesocyclops from varied geographical locations was tested against water content in sediment, temperature, and photoperiod. Trays containing sediment were inoculated with copepods and allowed to dry out for a period of 2 months and then reflooded. Both copepodids and adults of all species tested displayed desiccation resistance, with water content having greatest effect on survival.

Animals↗
PubMed1993

Role of natural killer cells in the pathogenesis of human acute graft-versus-host disease.

Clinical acute graft-versus-host disease (aGVHD) was correlated with alterations in PBL phenotype and skin immunohistology in 52 patients transplanted with HLA-identical bone marrow. Concurrent with the emergence of aGVHD, there was a profound decrease in absolute number of CD3- T cells and an increase in CD3-CD16+, CD56+ (a subset of which coexpress CD8+ "dim") NK cells in the PBL. CD4+ T and CD20+ B lymphocytes failed to recover within 90 days in the patients with grades II-IV aGVHD. Ex vivo partial T cell depletion, in itself, did not significantly impair T cell recovery as compared to that in non-T-depleted recipients unless aGVHD occurred. Although leukocytic cellular infiltration in the skin was generally sparse, CD16+ NK lymphocytes were significantly increased in grades II-IV aGVHD. By contrast, there was no significant increase in CD3+, CD4+, or CD8+ lymphocytes in these lesions as compared to skin biopsies obtained from BMT patients without aGVHD or from normal skin. Taken together, these findings suggest that NK cells may be important in the pathogenesis of human aGVHD.

Acute Disease↗
PubMed1993

Acute graft-versus-host-like disease induced by transplantation of human activated natural killer cells into SCID mice.

Whereas T lymphocytes are essential for the initiation of acute graft-versus-host disease (aGVHD), it is not at all clear whether they or other cells or noncellular factors actually mediate the characteristic lesions. This report describes the in vivo effects of human NK cells, T cells, and cytokines on the induction of aGVHD in 4 Gy sublethally irradiated C.B-17 scid/scid (SCID) mice. Human NK and T lymphocytes were obtained separately by antibody- and complement-mediated negative selection from the peripheral blood of normal donors and expanded in medium containing rIL-2 and irradiated autologous feeder cells. The characteristics of the two groups of cells were analyzed before injection into SCID mice. Cytofluorometric phenotyping demonstrated that 70-95% of NK-enriched cells expressed CD3-, CD16+, CD56+, and CD8-dim+; ninety-seven per cent of T cells expressed CD3+, TCR-alpha/beta+, CD4+, or CD8-bright+. Analysis of K562 and Daudi cultured target cell lines demonstrated 40-50% higher cytotoxicity by NK-enriched cells as compared with activated T lymphocytes. TNF-alpha cytokine production was greatly increased in activated NK cells (250 pg/ml) as compared with T cells (25 pg/ml) and fresh PBMC (12.5 pg/ml). IFN-gamma was increased in both NK and T cells. After i.v. injection of 1-5 x 10(7) cells into irradiated SCID mice, minor to severe skin lesions, diarrhea, and weight loss occurred in NK- but not the T cell-injected animals. In NK-injected animals, thinning and focal loss of epithelium with pyknotic nuclear change and degeneration and loss of skin appendages were observed. Single cell necrosis, crypt abscess formation, and loss of glandular epithelium developed in the colon of NK but not in T cell-injected animals. These findings are very similar to allogeneic aGVHD in SCID mice injected with C57BL/6 mouse splenocytes. Immunohistological staining with anti-human CD56, CD3, TNF-alpha, and IFN-gamma antibodies demonstrated CD56+ cells in association with TNF-alpha and IFN-gamma secretion in the bowel of NK-injected animals. CD3+ cells were not found in the same tissues. These findings were not observed in T cell-injected and control mice. In summary, aGVHD-like lesions were induced by transplantation of xenogeneic human activated NK cells into SCID mice. We hypothesize that cytokines released from human NK cells play a central role in the pathogenesis of clinical aGVHD.

Acute Disease↗
PubMed1993

Thy1+ bone marrow cells regulate the induction of murine syngeneic graft-versus-host disease.

A syngeneic graft-versus-host disease (GVHD)-like syndrome has been shown to be inducible in some strains of mice after lethal irradiation, reconstitution with syngeneic bone marrow (BM), and treatment with a short course of CsA therapy. Since Thy1+ BM cells have been shown to regulate the development of other experimental autoimmune diseases, it was important to determine their role in the inducibility of syngeneic GVHD (SGVHD) in different strains of mice. Lethally irradiated mice were reconstituted with either syngeneic BM or T cell-depleted syngeneic BM, then treated with CsA or diluent. Removal of Thy1+ cells from BM before reconstitution of an inducible strain, C3H/HeN, exacerbated SGVHD when compared with animals given whole BM cells before CsA treatment. Furthermore, a noninducible strain, C57BL/6 mice, developed SGVHD when reconstituted with T cell-depleted syngeneic BM but not BM before CsA therapy. These results suggest that Thy1+ BM cells may regulate the development of SGVHD, and be of importance in controlling autoreactivity after bone marrow transplantation.

Animals↗
PubMed1992

DNA cytometry in postirradiation cervical-vaginal smears.

Benign radiation change (BRC) in cervical-vaginal smears may be difficult to distinguish from postirradiation dysplasia (PRD) or recurrent cervical carcinoma. The utility of DNA analysis in postirradiation smears was evaluated retrospectively in 71 patients. Representative Papanicolaou smears were restained with a Feulgen method and 100 to 250 cells were analyzed for DNA content using the CAS 200 image analysis system. Thirty-three control irradiated patients had negative smears with a minimum 3-year follow-up. Thirty controls (91%) had diploid histograms with a mean coefficient of variation of 8.2% and an average of 6.8% of cells in S and G2/M phase. Three control patients had atypical nondiagnostic histograms. Twenty-three patients had abnormal smears and subsequent local recurrence; 21 (91%) had abnormal histograms, with seven showing polyploidy and 14 showing aneuploidy. The remaining 15 patients had abnormal smears diagnosed as PRD but no evidence of recurrent carcinoma. Five were polyploid, six were aneuploid, one was diploid, and three were atypical but nondiagnostic. Interactive DNA cytometry is useful in differentiating BRC from PRD and recurrent cancer. Aneuploidy is rarely, if ever, seen in negative smears with BRC. However, BRC may be associated with broad diploid peaks and increased proliferating cells. An abnormal histogram can be seen with PRD and does not always correlate with recurrent disease.

Adult↗
PubMed1991

Coumarin (1,2-benzopyrone) enhances DR and DQ antigen expressions by peripheral blood mononuclear cells in vitro.

Coumarin (1,2-benzopyrone) is a natural substance that appears to have some clinical activity against renal cell carcinoma and malignant melanoma. Preliminary evidence from in vitro and in vivo studies suggests that coumarin possesses immunomodulatory activity. It was reported previously that coumarin therapy resulted in augmented DR antigen expression by peripheral blood monocytes in cancer patients. The purpose of the present study was to examine the effects of coumarin on DR and DQ antigen expression by normal donor peripheral blood mononuclear cells in vitro. Using monoclonal antibody labeling techniques and FACS analysis, it was shown that both DR and DQ antigen expression by peripheral blood mononuclear cells were enhanced over controls after 48 hours of exposure to coumarin. While monocytes normally express these antigens, enhanced expression is consistent with an activated state. These results support the hypothesis that coumarin acts, at least in part, through immune augmentation.

Cells, Cultured↗