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Biomedical subjects

J R Fischer

Publications and source records attributed to J R Fischer.

At least 19 recordsLinked to original sources

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

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

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

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

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

Cutaneous neoplasia in 340 cats.

A total of 340 cases of cutaneous neoplasia were diagnosed in 340 of 3,564 cats that were examined by biopsy or necropsy during a 41-month period from January 1, 1986 through May 31, 1989. Eighteen types of tumor occurred, but four types comprised 77% of the cases. These were basal cell tumor, 89 cases (26%, mean age 10.3); mast cell tumor, 72 cases (21%, mean age 8.6); squamous cell carcinoma, 52 cases (15%, mean age 11.6); and fibrosarcoma, 50 cases (15%, mean age 10.2). For each of these four types of tumors, peak number of cases occurred in cats older than 10 years. Mast cell tumor was the only tumor diagnosed in cats younger than 1 year. The head was the most common site for basal cell tumors, mast cell tumors, and squamous cell carcinomas. The legs were the most common location of fibrosarcomas. Siamese cats had approximately three times as many mast cell tumors as statistically expected, but only one-fourth as many squamous cell carcinomas. Breed predilection for other skin tumors was not apparent. Sex predilection was not detected for any skin tumor.

Animals

Biology and clinical use of GM-CSF in lung cancer.

Administration of granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to induce an increase in production of neutrophils, monocytes, and eosinophils. This is reflected in an accelerated recovery of myelopoiesis following cytotoxic chemotherapy and radiation. Human trials completed so far have used patients with many tumor types. It was clearly demonstrated that the leukocyte responses are dose and schedule dependent and that the route of factor administration is important. The results of clinical trials suggest that the acute toxicity of cytotoxic chemotherapy may be decreased. This may result in a higher dose of drugs or in a reduction of treatment interval, and it may increase the rate of complete remissions and the number of patients with long-term disease free survival, particularly in small cell lung cancer. However, up to now a definitive statement as to the value of this supportive treatment in solid tumor chemotherapy is not possible.

Carcinoma, Small Cell

Blast-like cells in cerebrospinal fluid of neonates. Possible germinal matrix origin.

Primitive cell clusters (PCCs) composed of immature blast-like cells were observed in Wright's-stained cerebrospinal fluid (CSF) cytocentrifuge specimens from four infants over an 18-month period. All of these patients had hydrocephalus; in three this was secondary to subependymal germinal matrix intraventricular hemorrhage (IVH) associated with prematurity. The fourth was associated with Arnold-Chiari malformation, Chiari type II. In the CSF samples from the patients with IVH, hemosiderin-laden macrophages were also prominent and, in some cases, were intimately admixed with the PCCs. Immunoperoxidase staining of cytocentrifuge preparations from one of the patients revealed that the PCCs stained with neuron-specific enolase (NSE) but not with pan-leukocyte antibodies. Cells with similar morphologic characteristics to PCCs in the CSF of infants have been infrequently illustrated in the literature and thought to be of hematopoietic origin. However, the immunohistochemical findings and the clinical presentation suggest that PCCs are most likely germinal matrix cells.

Arnold-Chiari Malformation

Intraparotid nodular fasciitis.

We describe two cases of nodular fasciitis arising within the parotid glands of two patients, a 42-year-old man and a 2 1/2-year-old boy. The clinicopathologic, immunohistochemical, and ultrastructural features of this lesion and its differential diagnosis are discussed.

Adult

Recovery to +1Gz and +2Gz following +Gz-induced loss of consciousness: operational considerations.

With the development of aircraft autorecovery technology, the need to understand the effects of potential inflight recovery profiles on human physiology has become important. Eight male volunteer subjects were exposed to +7Gz with an onset rate of 6 G.s-1 until they were unconscious. The subjects did not wear anti-G suits and did not perform anti-G straining maneuvers. The subjects controlled the centrifuge utilizing an F-16A stick, thereby deliberately self-inducing their unconsciousness. Following +Gz-induced loss of consciousness (G-LOC), recovery to the usual +1Gz level was compared to recovery to a +2Gz level by comparing absolute, relative, and total incapacitation times. The mean (+/- S.D.) absolute incapacitation time (period of unconsciousness) was 11.9 +/- 2.9 s for recovery to a +1Gz level and 12.9 S (+/- 6.9 S.D.) for recovery to a +2Gz level. The mean relative incapacitation time (period of confusion/disorientation) was 3.6 +/- 2.3 s for recovery to a +1Gz level as compared to 2.9 +/- 0.8 s for recovery to a +2Gz level. The total incapacitation time (sum of the absolute and relative incapacitation) was 15.6 +/- 2.7 s for recovery to a +1Gz level and 16.0 s (+/- 6.8 S.D.) for recovery to a +2Gz level. No significant differences in any of the incapacitation times were found when comparing recovery to +1Gz and +2Gz. The mean time from the onset of +Gz-stress to the onset of unconsciousness was approximately 7 s.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The relationship of serum IgA concentration to human immunodeficiency virus (HIV) infection: a cross-sectional study of HIV-seropositive individuals detected by screening in the United States Air Force.

Serum immunoglobulins were measured in 107 patients with human immunodeficiency virus seropositivity. Each patient was categorized by the Walter Reed staging classification and serum concentrations of immunoglobulins were compared with patient staging. Serum IgM concentrations were normal in all but nine patients. Serum IgG concentrations were elevated in 74 of 107 patients, with no significant differences noted between different stages of disease severity. Serum IgA concentrations were elevated in 38 of 107 patients, with a significant relationship noted between increasing staging category and increasing serum IgA concentration (p = 0.0001). Serum IgA concentrations in patients with human immunodeficiency virus seropositivity may be a useful marker of immunologic progression of disease.

Acquired Immunodeficiency Syndrome

Decompression sickness and bubble formation in females exposed to a simulated 7.8 psia suit environment.

The purpose of this study was to measure female susceptibility to decompression sickness (DCS) during simulated extravehicular activity (EVA) at a candidate (7.8 psia) suit pressure. Thirty female volunteer subjects, in groups of three, were exposed to three consecutive daily EVA simulations at 7.8 psia (5,031 m altitude equivalent) continuously for 6 h. During each altitude exposure, the subjects breathed a gas mixture of 50% oxygen/50% nitrogen, and participated in exercise workloads similar to those expected to be experienced by astronauts during a typical EVA scenario. Precordial Doppler bubble monitoring was accomplished after each cycle of exercise workload simulations. During at least 1 of the 3 days (d) of exposure, 43% of the subjects experienced intravenous bubbling. Of the 30 subjects, 17 (57%) did not experience detectable bubbling on any of the 3 d of exposure and 5 (17%) developed decompression sickness (DCS) during the study. Two cases were delayed, occurring after recompression to ground level; and three subjects required hyperbaric oxygen treatment. The results of this study suggest that female subjects may suffer more delayed DCS symptoms, necessitating hyperbaric oxygen treatment, than their male counterparts under the same experimental conditions. Female subjects did not experience intravenous bubbling as frequently as male subjects when exposed to these study conditions.

Adult

Thrombolysis of peripheral arterial and graft occlusions: improved results using high-dose urokinase.

Ninety-three thromboembolic occlusions of peripheral arteries or grafts in 85 patients were treated with high-dose urokinase by direct intraarterial infusion. Urokinase was infused at 4000 IU/min until antegrade blood flow was reestablished and then at 1000 or 2000 IU/min until clot lysis was completed. Of the 93 infusions, 75 (81%) resulted in clinical improvement. The infusion therapy was incomplete in nine patients. The mean duration of the 84 completed infusions was 18 +/- 20 hr, the incidence of complete clot lysis was 83%, and the incidence of clinical improvement was 89%. Significant bleeding, requiring transfusion, occurred during or after four of the urokinase infusions (4%). Other complications included distad clot migration, thrombus formation on the catheter, revascularization phenomena, oliguria, skin rash, pseudoaneurysm, balloon rupture during angioplasty, and vascular spasm. There were no instances of drug resistance or adverse drug reactions. These results indicate that an initially high-dose urokinase regimen accomplishes more rapid recanalization, a higher incidence of total clot lysis, and produces fewer complications than the standard low-dose streptokinase regimen.

Catheterization

Rumen fermentation characteristics, nitrogen balance and growth in lambs fed methane digester effluent.

A laboratory silo trial, two lamb metabolism trials and a lamb growth trial were conducted to compare the nitrogen (N) value of swine methane digester effluent (MDE) to that of urea. Using laboratory silos (four/treatment), fermentation characteristics were measured for silages containing cracked corn, ground wheat straw and MDE added at levels of 0, 4, 8 or 12% of silage dry matter (DM). Lactic acid concentration increased linearly with up to 8% MDE addition, but then decreased (P less than .05; quadratic) with 12% MDE. Butyric acid was highest (P less than .05; linear) with 12% MDE, indicating an undesirable fermentation. In a metabolism study, DM, organic matter and N digestibilities and N balance were similar (P greater than .10) between urea and MDE, but DM digestibility was lower (P less than .05) for ensiled diets (52%) than diets fed fresh daily (59.4%). Mean ruminal volatile fatty acid, ruminal ammonia-N and plasma urea-N concentrations were similar (P greater than .10) between urea- and MDE-fed lambs. Plasma urea-N was higher (P less than .05) and ruminal isovaleric acid lower (P less than .05) in animals fed ensiled than fresh diets. In the second metabolism trial, digestibility of N was lowest (P less than .05) for MDE (51.2%) and highest for soybean meal (SBM; 71.8%), but N balance was similar among all diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed