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Biomedical subjects

J R Fischer

Publications and source records attributed to J R Fischer.

18 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

Suicide and alcoholism. Interpersonal loss confirmed as a predictor.

We earlier reported that nearly one third of a consecutive series of 31 alcoholics who committed suicide had experienced loss of a close interpersonal relationship within six weeks or less of their death. In a replication study of 50 additional unselected alcoholic suicides, we found that 26% had experienced such loss within six weeks. As before, the distribution of such events was strikingly and significantly skewed toward the final weeks of the subject's life. This powerful confirmation gives added significance to such loss as a predictor of suicide among alcoholics.

Adult

Normal electrocardiographic waveform characteristics during treadmill exercise testing.

Forty asymptomatic male patients at low risk for cardiovascular disease completed maximal treadmill testing. Electrocardiograms from leads CC5, CM5, V5, Yh and Z were recorded across multiple pretest, exercise and recovery conditions. ECG waveforms were subsequently digitized, averaged and processed to provide Q-, R-, S- and T-wave amplitudes, ST-segment means and slopes, and QS- and RT-interval durations. Average R-wave amplitude increased during early exercise and then dramatically decreased to maximum effort. Average S-wave amplitude became greater as exercise progressed. Average J junction was slightly positive before exercise, became negative during exercise (except lead Z) and returned to zero after exercise. The ST-segment slope increased dramatically with progressive exercise. The response of T-wave amplitude, RT and QS intervals are also described. Separately, 22 asymptomatic male subjects each completed two maximal treadmill tests 2 weeks apart. ECG data acquisition and processing were similar to those noted above. Pooled, within-subject estimates of variability were computed for the ECG leads, ECG measurements and protocol conditions. These variability estimates are useful for interpreting ECG responses to exercise testing.

Adult

Blood pressure variability of the individual in orthostatic testing.

Within-subject blood pressure (BP) variability was studied in the context of orthostatic testing. Nineteen healthy men volunteered for biweekly orthostatic testing. BP's were taken on alternate minutes during 5 min of supine rest and a subsequent 5 min of quiet standing. Within-subject variance was computed for systole and diastole by protocol condition; respective variances were than pooled (i.e. averaged) across subjects. The within-subject estimate of variance for a single BP reading in either position was approximately 6 torr (i.e. 1 S.D.). This variance estimate was reduced by averaging additional BP readings from the same visit, and more so by averaging BP readings from multiple visits. These findings have use in the design of orthostatic protocols and in the interpretation of BP data derived therefrom.

Adult

On internal electron transfer in xanthine oxidase.

The structural basis for intramolecular electron transfer in xanthine oxidase (EC 1.2.3.2) has been probed using temperature-jump perturbation and optical spectroscopic methods. Redox equilibria were found to be temperature-insensitive; hence it is argued that electron transfer is not accompanied by any extensive macromolecular conformational changes. No evidence for absorption phenomena ascribable to optical electron transfer could be found throughout the course of reductive titration of the biological particle. The combined results suggest that long-range electron transfer in the xanthine oxidase can best be described as occurring between only weakly interacting redox sites embedded in a rigid protein matrix.

Animals

Pregnancy after jejunoileal bypass and the SGA infant.

Twenty-one pregnancies (19 patients) were studied, noting the effects of previous jejunoileal bypass on perinatal sequelae. A larger percentage of SGA infants (20%) were delivered to mothers after bypass surgery. Low birthweight appears to be related to maternal hypoalbuminemia. Twelve of thirteen (92%) infants born to multiparous patients after surgery had term birthweights less than any previous term infant's birthweight prior to the procedure. Postponement of pregnancy after ileal shunt until all metabolic parameters have returned to normal (up to 36 months) is advised.

Adult

Characterization of a cell-lethal product from the photooxidation of tryptophan: hydrogen peroxide.

Near-ultraviolet (300 to 400 nanometers) irradiation of saturated, oxygenated solutions of tryptophan in the absence of added sensitizer gives rise to substances that have various biological effects on isolated cells, including mutagenicity and selective lethality to recombination-deficient bacterial mutants. One of these biologically active products has been identified as H2O2, on the basis of spectrometric, chromatographic, chemical, and biological properties. Now H2O2 has been shown to account for the biological activities mentioned above.

Escherichia coli

The effect of aging on the impact resistance of heat tempered lenses.

Stock sperocylindrical lenses (125) with approximately 2.2-mm center thickness were bevel-edged to 48-mm size in the S-10 standard military lens shape. One time each, 25 lenses were drop balled directly after heat treatment; 25 after 3 months;25 after 6 months; 25 after 9 months; and the final 25 after 1 year. Comparing these samples against each other showed no statistical difference in breakage. All the surviving lenses were then drop balled repeatedly until broken or 25 impacts had been made. After 25 hits, 76.8% of the lenses did not break. There was no statistical difference in breakage when these results were compared with 125 heat-treated lenses of similar specifications that were drop balled for 25 trials, if not broken sooner, just after routine heat-treatment processing. Lenses of approximately 3.0-mm center thickness, with other aspects the same, were also treated. The effect of drop balling nonheat-tempered lenses of dimensions similar to the aged lenses was studied; the first drop had a casualty rate of 75%, and no lens survived more than 8 impacts.

Eyeglasses

Membrane filter technique for enumeration of enterococci in marine waters.

A membrane filter procedure is described for the enumeration of enterococci in marine waters. The procedure utilizes a highly selective and somewhat differential primary isolation medium followed by an in situ substrate test for identifying colonies of those organisms capable of hydrolyzing esculin. The procedure (mE) was evaluated with known streptococci strains and field samples with regard to its accuracy, sensitivity, selectivity, precision, and comparability to existing methods. Essentially quantitative recovery was obtained with seawater-stressed cells of Streptococcus faecalis and S. faecium. Neither S. bovis, S. equinus, S. mitis, nor S. salivarius grew on the medium. The selectivity of the medium was such that a 10,000-fold reduction in background organisms was obtained relative to a medium which contained no inhibitors and was incubated at 35 C. About 90% of those typical colonies designated as enterococci confirmed as such and about 12% of the colonies not so designated were, in fact, identified as enterococci. Plate to plate variability across samples approximated that expected by chance alone. Verified recoveries of enterococci from natural samples by the mE procedure, on the average, exceeded those by the KF method by one order of magnitude.

Cell Count