Search PubMed⌕ Search

Biomedical subjects

J R Fischer

Publications and source records attributed to J R Fischer.

At least 55 records · Page 3Linked to original sources
PubMed1995

Aflatoxin contamination of corn used as bait for deer in the southeastern United States.

Samples of shelled corn used for wildlife feed were taken from bait piles and storage bins in North Carolina and South Carolina (USA) from 29 September through 28 November 1993, and were analyzed for aflatoxin. Twenty (51%) of 39 samples were positive, with aflatoxin levels ranging from a trace to 750 parts per billion. Based on the high prevalence of aflatoxin-contaminated corn, exposure of wild-life to aflatoxin undoubtedly occurs, although the effects of such exposure are largely unknown.

Aflatoxins↗
PubMed1995

Interleukin 4 down-regulates expression of c-kit and autocrine stem cell factor in human colorectal carcinoma cells.

Stem cell factor (SCF) is a cytokine which plays an important role in the development of precursor cells. We have investigated the expression of SCF and its receptor, the c-kit proto-oncogene, in human colorectal carcinoma cell lines. Using reverse transcription-PCR, we confirmed the expression of c-kit in two lines (LS174T and LS1034) and of SCF in 9 of 11 cell lines tested. In a Northern blot, a single transcript of 6.6 kb was detected for SCF mRNA. In addition, two lines (LS174T and HT29) synthesized SCF protein, as detected by Western blot analysis. SCF stimulated proliferation and colony formation of LS174T in a dose-dependent manner up to 160%. A half-maximal effect was obtained with about 5.5 ng/ml of SCF under both growth conditions. LS174T cells expressed the M(r) 145,000 c-kit protein on the cell surface and a neutralizing anti-c-kit mAb inhibited colony formation of LS174T by 40%. Interleukin 4 (IL-4) completely inhibited SCF-induced proliferation of LS174T cells. Interestingly, IL-4 induced an almost complete down-regulation of both c-kit and SCF expression in LS174T. Our findings suggest that in LS174T cells, an SCF-mediated autocrine loop is functional and that IL-4 down-regulates the expression of both the receptor and the ligand of this circuit.

Base Sequence↗
PubMed1994

Growth inhibition of human colorectal-carcinoma cells by interleukin-4 and expression of functional interleukin-4 receptors.

The growth-inhibitory effect of interleukin-4 (IL-4) was investigated in a panel of 7 human colorectal-carcinoma cell lines. In 5 cell lines (HT29, WiDr, LS411N, LS513, LS1034) a dose-dependent reduction of proliferation was documented. At 100 U/ml, IL-4 inhibited thymidine incorporation between 45 and 75% and MTT conversion (26 to 41%). The ability of LS513 and WiDr cells to form colonies after IL-4 treatment was reduced by 85 and 62% respectively. LS513 was the most sensitive cell line, with IL-4 inducing half-maximal inhibition at 5 to 6 U/ml. The inhibitory effect of IL-4 was completely neutralized by anti-IL-4 antibodies. Northern-blot analysis revealed the presence of IL-4-receptor (IL-4R) mRNA in all cell lines. The membrane expression of the 130-kDa IL-4R was assessed by FACS, utilizing an anti-IL-4R monoclonal antibody and was confirmed by biotinylated IL-4 binding. Our results attribute an important role for IL-4 as a negative regulator of colorectal-carcinoma cell growth, thus indicating a possible avenue for intervention in this disease.

Blotting, Northern↗
PubMed1994

Blockade of the insulin-like growth-factor-I receptor inhibits growth of human colorectal cancer cells: evidence of a functional IGF-II-mediated autocrine loop.

Insulin-like growth factors (IGFs) are potent proliferation stimulators for numerous tumor cells and often function as autocrine growth factors. We have previously shown that exogenous IGF-I and IGF-II enhance proliferation of colorectal carcinoma cells. The biological signal of both factors is transmitted through the IGF-I receptor (IGF-I-R). This receptor was expressed in 12/12 colorectal carcinoma cell lines tested. alpha IR3, a neutralizing monoclonal antibody (MAb) directed against the human IGF-I-R, inhibited proliferation in 7/12 lines (Caco-2, HT-29, LS411N, LS513, LS1034, WiDr and SW620), as reflected by a reduction of MTT conversion (19 to 42%), a decrease in cell number (39 to 72%) and an increase in doubling time (up to 2-fold). In addition, in 4 cell lines (Caco-2, LS513, LS1034, WiDr) alpha IR3 suppressed colony formation in methylcellulose (40 to 84%). Excess of exogenous IGF completely neutralized alpha IR3-mediated inhibitory effects. Northern blot analysis revealed abundant expression of 2 IGF-II transcripts of 5.0 and 4.3 kb in LS1034 cells. In addition, we observed that growth inhibition by alpha IR3 was correlated with a more differentiated phenotype. Our results suggest that growth of many colorectal carcinoma cell lines is regulated by autocrine IGF-II-mediated stimulation of the IGF-I-R.

Antibodies, Monoclonal↗
PubMed1994

Secretion of bioactive granulocyte-macrophage colony-stimulating factor by human colorectal carcinoma cells.

Secretion of several cytokines by colorectal carcinoma cells has been substantiated. These do not include granulocyte-macrophage colony-stimulating factor (GM-CSF) thus far. We show that the supernatant of two human colorectal carcinoma cell lines, LS1034 and SW480, stimulates proliferation of GM-CSF-dependent M07e cells. The activity was constitutively secreted by LS1034 cells and could be induced by serum-free culture conditions in SW480 cells. Addition of a neutralizing anti-GM-CSF antibody completely inhibited this activity. Preabsorption with anti-GM-CSF antibody removed all M07e growth-stimulating activity from LS1034 and SW480 supernatant. Western blot analysis revealed the presence of GM-CSF in LS1034 supernatant. Our results indicate that human colorectal carcinoma cells secrete indeed biologically active GM-CSF.

Colorectal Neoplasms↗
PubMed1994

Constitutive secretion of bioactive transforming growth factor beta 1 by small cell lung cancer cell lines.

We investigated effects of soluble mediators secreted by small cell lung cancer (SCLC) cell lines on modulation of cytokine-induced growth of lymphocytes. We found that interleukin-2 (IL-2)-mediated T-cell growth was inhibited by a cytokine constitutively secreted by the SCLC cell line, NCI-N417. Of several cytokines tested, only transforming growth factor beta 1 (TGF beta 1) severely suppressed IL-2-dependent T-cell growth. Using a specific anti-TGF beta 1 antibody, we found that this antibody blocked the immunosuppressive activity secreted by NCI-N417. Thus, the NCI-N417-derived immunosuppressive molecule was serologically identified as TGF beta 1. Further experiments showed that TGF beta 1 was secreted by four of eight SCLC lines tested. mRNA for TGF beta 1 was expressed in NCI-N417 and in SCLC-22H. Constitutive secretion of biologically active TGF beta 1 by SCLC lines suggests that tumour-derived immunosuppression may have clinical relevance.

Carcinoma, Small Cell↗
PubMed1994

Immunohistochemical staining of feline malignant fibrous histiocytomas.

Malignant fibrous histiocytoma was diagnosed in seven cats from biopsy specimens received at the University of Missouri Veterinary Medical Diagnostic Laboratory during a 4-year period from 1987-1991. Tissue blocks from formalin-fixed specimens were resectioned and stained for type I (AE1) and type II (AE3) cytokeratins, desmin, S100 protein, vimentin, and alpha 1-antitrypsin by the avidin biotin peroxidase complex method with diaminobenzidine (DAB) chromogen. None of the tumors stained positively for alpha 1-antitrypsin. Four of seven of the tumors had similar immunohistochemical staining results, with positive staining for type I and type II cytokeratins, desmin, S100 protein, and vimentin. Of the remaining three, one stained positively only for S100 protein and vimentin; one stained positively for vimentin only; and one was negative for all six antigens. Based only on immunohistochemical staining results, three of the tumors could possibly be reclassified: one as a melanoma, one as a probable fibrosarcoma, and one as unknown. These results also indicate that feline malignant fibrous histiocytomas show a diversity of intermediate filament expression, as do human tumors. Our results also do not support the theory that malignant fibrous histiocytomas are of histiocytic origin.

Animals↗
PubMed1994

Induction chemotherapy with and without recombinant human granulocyte colony-stimulating factor support in locally advanced stage IIIA/B non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) in stage IIIA with more than minimal N2 involvement or in stage IIIB are considered unresectable. Response rates to chemotherapy for these patients are in the range of 40%. Reduction of tumor mass by induction chemotherapy may lead to resectability and to improved survival. We evaluated response rates and determined influence of induction chemotherapy on survival when followed by surgery and radiotherapy in 60 patients with primarily inoperable stage IIIA/IIIB NSCLC. The following cytotoxic regimens were used: cisplatin (100 mg/m2) and vindesine (3 mg/m2); ifosfamide (10 g/m2) and etoposide (360 mg/m2); or a combination of cisplatin (75 mg/m2), ifosfamide (6 g/m2), and etoposide (360 mg/m2). Sixty patients were treated with two to four cycles of these regimens between June 1988 and October 1992. In 40 patients chemotherapy was repeated every 4 weeks. In 20 patients chemotherapy was intensified by interval reduction to 3 weeks with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) support. The median patient age was 54 years, and Eastern Cooperative Oncology Group performance status was 0 to 2. Distribution of stages IIIA and IIIB was 21 and 39 in all patients and 5 and 15 in the group treated with r-metHuG-CSF support, respectively. The overall response rate (complete plus partial responses) was 35%. In patients treated with intensified chemotherapy and r-metHuG-CSF support, the response rate was 60%. In 37 patients (61.6%) tumor was resected 4 to 6 weeks after the last cycle of chemotherapy; R0 resection was achieved in 22 patients, R1 in eight patients, and R2 in seven patients. With a follow-up of 4 to 60 months, 1-year survival in patients with tumor regression after chemotherapy and tumor resection was 82.2% versus 35.7% in nonresponders; 2-year survival of responders and nonresponders was 50.9% and 12.8%, respectively; and median survival was 23 months and 9 months, respectively (P < .001). Median survival rates for responders with stage IIIA and IIIB disease were 39 and 17 months, respectively. Median survival after response to chemotherapy and incomplete resection (11 patients) was 17 months, whereas median survival after response to chemotherapy and complete resection (18 patients) has not yet been reached. Only four patients in this group have died with a follow-up of 4 to 60 months. Of 20 patients receiving accelerated chemotherapy with r-metHuG-CSF support, World Health Organization grades 3 and 4 neutropenia occurred in five and eight patients, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Growth stimulation of a human colorectal carcinoma cell line by interleukin-1 and -6 and antagonistic effects of transforming growth factor beta 1.

We analysed the effect of interleukin-1 (IL-1), IL-6 and transforming growth factor beta 1 (TGF beta 1) on the growth of a panel of eight colorectal carcinoma cell lines. IL-1 stimulated growth of two lines (LS411N and LS1034) up to 20-fold and IL-6 enhanced proliferation of LS1034 more than 5-fold. Both cytokines also augmented colony-formation of LS1034 in methylcellulose. Under both growth conditions IL-1 was the most potent stimulator. However, the addition of IL-6 to IL-1 synergistically enhanced proliferation of LS1034 in monolayer culture and additively augmented the number of colonies formed in methylcellulose. Furthermore, TGF beta 1 strongly reduced the growth rate of LS1034. Low amounts of TGF beta 1 markedly inhibited the response of LS1034 to IL-1 and totally abrogated proliferation induced by IL-6. We conclude that different cytokines can provide distinct signals for the regulation of growth of colorectal carcinoma cells.

Cell Division↗
PubMed1992

Growth regulation and co-stimulation of human colorectal cancer cell lines by insulin-like growth factor I, II and transforming growth factor alpha.

We have tested growth factor responsiveness of a panel of eight human colorectal carcinoma cell lines. Insulin-like growth factors I and II (IGF-I and IGF-II) stimulated growth of five lines (HT-29, LS411N, LS513, SW480, WiDr). At 30 ng ml-1 both factors enhanced growth up to 3-fold. They induced half-maximal stimulation at 1.9-6.51 ng ml-1. Even after delayed addition IGF-I and II significantly enhanced growth in a short-term proliferation assay. They exerted maximal effects under limiting serum conditions (0.5% FCS) and at low cell density (1.25-5 x 10(4) ml-1). Using these conditions transforming growth factor alpha (TGF alpha) enhanced proliferation of all IGF-responsive cell lines, except SW480. 1.11-3.31 ng ml-1 were required to obtain a half-maximal response. With 10-20 ng ml-1 maximal stimulation occurred at plateau values different from those for IGF-I/II. Proliferation of all cell lines responsive to both IGF-I and TGF alpha was further enhanced by combining both factors, resulting a synergistic response of LS513, while the effects on HT-29, LS411N and WiDr were additive. With HT-29 and LS411N a 24 h exposure to TGF alpha was sufficient to obtain a full response in the co-stimulatory assay. Our results illustrate the importance of IGF-I/II and TGF alpha as stimulators of growth of colorectal carcinomas.

Cell Division↗
PubMed1992

Oral ifosfamide-mesna: a clinical investigation in advanced non-small-cell lung cancer.

The purpose of this study was to evaluate the toxicity and response efficacy of fixed-dose oral ifosfamide (OI)-mesna (M) in advanced, non-small-cell lung cancer (NSCLC). OI was given in four different fractionated-dose treatment schedules with a total dose per cycle of either 3.0 g/m2, 6.0 g/m2, 7.5 g/m2 or 10 g/m2 (equivalent to a daily dose of either 750 mg, 1000 mg or 1250 mg.) M was given p.o. by drinking ampules. In the 64 patients (pts) included, a total of 305 treatment cycles were administered with no evidence of severe neurotoxicity. Twenty-two pts (37%) developed mild to moderate CNS toxicity. Neither myelosuppression, alopecia, gastrointestinal toxicity nor urotoxicity were clinical problems. On schedule 2 (6 g/m2), 3 of 14 evaluable pts (21%) had partial remissions (PR), and on schedule 3 (7.5 g/m2) 4 pts (25%) showed PRs. The median duration of response was 9 months (mts) for pts on schedule 2, and 8 mts for pts on schedule 3. We conclude that OIM can easily be tolerated in the same dose usually given intravenously (7.5 g/m2/mts), when patients at high risk for developing CNS toxicity have been previously excluded from therapy. In order to reduce CNS toxicity, it is suggested that the total dose per cycle should not exceed 7.5 g/m2 (1000 mg daily) within a fractionated-dose, 14-day treatment schedule. We further conclude that the tumor response efficacy of OIM in NSCLC is comparable to the one achieved by intravenously-administered IM, whereby the total monthly OI dose should not be less than 6.0 g/m2 (750 mg daily).

Aged↗
PubMed1991

Salmonella typhimurium abscess as a postoperative complication in a horse with colic.

An 11-year-old, 430-kg fox-trotter stallion was referred for evaluation of colic. A right-sided inguinal hernia was diagnosed. At exploratory laparotomy, the ileum was found to be herniated through the right inguinal canal. Compromised small intestine was resected, jejunocecal anastomosis was performed, and the horse was castrated. Three days after surgery, the stallion would not bear weight on the left hind limb. The musculature of the left thigh region became swollen. Aspiration of the left thigh region yielded serosanguineous fluid from which Salmonella typhimurium was isolated. Ultrasonography of the left thigh revealed multiple hypoechoic areas suggestive of abscess. The left medial thigh region was surgically incised, and a large abscess was drained. Bacteriologic culture of feces yielded S typhimurium. The owner elected to have the horse euthanatized.

Abscess↗
PubMed1991

Effect of rhGM-CSF on haematopoietic reconstitution after chemotherapy in small-cell lung cancer.

In three consecutive pilot studies the effect of recombinant human granulocyte/macrophage-colony-stimulating factor (rhGM-CSF) on haematopoetic recovery after chemotherapy in patients with small-cell lung cancer was investigated. In study I, 20 patients received AIO chemotherapy (A, Adriamycin 25 mg/m2 on days 1 + 2; I, ifosfamide 2 g/m2 on days 1-5; O, vincristine 2 mg on day 1) at 4-week intervals either with or without rhGM-CSF (250 micrograms/m2 sc) from day 8 until recovery of leucocytes. Neither the degree nor the duration of myelosuppression was markedly influenced by rhGM-CSF. Suggesting that these disappointing results were caused by the late onset of GM-CSF application, in the following study we shortened chemotherapy to 3 days and started with GM-CSF on day 4. The main objective of this study was to test whether the earlier administration of GM-CSF allowed treatment intervals to be reduced or the dose to be escalated. After 10 patients had received a starting dose of AIO (A, 50 mg/m2 on day 1; I, 2 g/m2 on days 1-3; 0,2 mg on day 1) alternating with cisplatin (90 mg/m2 on day 1) and etoposide (150 mg/m2 on days 1-3), the dose of ifosfamide and etoposide was escalated to 2.5 g/m2 on days 1-3 and 200 mg/m2 on days 1-3 in the next 10 patients. Treatment was given at 2-week intervals when leucocytes were greater than 3500/mm3 and thrombocytes were greater than 100,000 mm3 on day 14. At each dose level patients were randomized to receive either rhGM-CSF 250 micrograms/m2 s.c. on days 4-12 or no GM-CSF. In this study, rhGM-CSF markedly shortened the duration of leukopenia. Reinstitution of chemotherapy on day 15 was possible at dose level 1 in 1/4 patients without and in 3/4 patients with GM-CSF, and at dose level 2 in 0/5 patients without and in 5/5 patients with GM-CSF. However, the degree of myelosuppression was not improved by GM-CSF. In a third study we tried to apply rhGM-CSF simultaneously with chemotherapy. After 3 patients had received GM-CSF starting on day 1 concurrent to AIO chemotherapy, we noticed an increase of myelosuppression with prolonged neutropenia and thrombocytopenia and stopped this investigation. Considering all patients included in these three consecutive pilot studies, there is no difference in response rates and survival between patients with and without rhGM-CSF treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗