Serum levels of tumor necrosis factor alpha in patients treated with granulocyte-macrophage colony-stimulating factor.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
C Weiss
Publications and source records attributed to C Weiss.
Serum levels of tumor necrosis factor-alpha in hairy cell leukemia.
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Humans↗
[The significance of the preoperative CEA value for the prognosis of rectal cancer].
254 patients were operated for rectal carcinoma in the period from 1980 to 1986. The number of curative procedures, recurrence rate and 5-year-survival rate were dependent on the preoperative CEA levels, which correlated with the tumour stage. Even within tumour stages with enough cases for statistical evaluation the CEA could be established as an independent prognostical variable. Within stage pT2N0M0 recurrence rate for patients with preoperative CEA level below 5 ng/ml was 29% compared to 64% in patients with higher serum levels. Median survival time for the two groups were 65 and 35 months, respectively. In stage of lymph node involvement median survival times of 46 and 25 months were observed for the groups with CEA levels above and below 5 ng/ml. The pattern of recurrence within the two stages seemed to be unaffected by the preoperative CEA level. Patients with preoperative elevated CEA represent a risk group with need of consistent postoperative follow-up and CEA controls.
Carcinoembryonic Antigen↗
Systematic variation in myosin expression along extraocular muscle fibres of the adult rat.
Monoclonal antibodies (McAB) specific for fast (C14) and slow (S58) myosin, and a myosin antigenically similar to neonatal/embryonic myosin in mammals (ALD180), were used to characterize the myosin distribution in orbital layer fibres of rat extraocular muscles (EOM) in relation to innervation patterns. The orbital layer is composed of both singly-innervated (SIF) and multiply-innervated (MIF) fibres. The SIFs have the characteristics of twitch fibres, while the MIFs, in addition to possessing many small endings characteristic of tonic fibres, also have an en-plaque-like innervation in the endplate band resembling that of the adjacent SIFs. Myosin expression in MIFs and SIFs is unusual and varies systematically along the length of the fibres. Both SIFs and MIFs label with ALD180, but this labelling is absent in both fibre types in the endplate band region, where all fibres label with C14. Distally and also proximally to the endplate band, SIFs label with both ALD180 and C14, while the MIFs, innervated by many small, superficial endings in these regions, label with ALD180 only. This pattern of myosin expression could also be demonstrated in isolated fibres. The results are discussed in relation to the hypothesis that both populations of orbital layer fibres express constitutively both fast and the neonatal-like myosin, and that superimposed on this constitutive expression twitch or tonic innervation acts locally to selectively suppress either neonatal-like or fast myosin, respectively.
Adenosine Triphosphatases↗
Prognostic significance of glucocorticoid receptor determination in patients with chronic lymphocytic leukemia and immunocytoma--lack of a positive correlation between receptor levels and clinical responsiveness.
Glucocorticoid receptors (GR) have been suggested to have prognostic significance in patients with CLL treated with chemotherapy containing glucocorticoid. In this study, the GR levels in 65 patients with advanced CLL and immunocytoma (clinical stages III and IV according to Rai) were determined by means of a whole cell assay. The median GR-level was 1,920 bs/c with a range from 0 to 9591. The patients were subsequently treated according to a prospective, randomized trial with either a combination of chlorambucil and prednisolone, or with prednimustine. No significant difference in receptor levels was found between responders (median = 1940 bs/c; n = 47) and nonresponders (median = 1950 bs/c; n = 14). To assess the influence of receptor content on prognosis we have analyzed the relationship between GR content and survival time and duration of response. There was no significant difference in duration of response and in survival between those patients with high (greater than 1920 bs/c) and those with low GR levels (less than 1920 bs/c) (log-rank test). Our data suggest that determination of GR provides no reliable indicator for clinical response to regimens with glucocorticoid as a component in patients with CLL and immunocytoma.
Adult↗
The use of postoperative irradiation for the prevention of heterotopic bone after total hip replacement with biologic fixation (porous coated) prosthesis: an animal model.
Radiation has been shown to be effective in the prevention of heterotopic bone. The exact etiology of heterotopic bone is unknown. Total Hip prosthetic devices that do not depend upon bone cement for fixation have become increasingly popular. The mechanism by which the bone forms around the prosthesis is similar to the process by which fractures heal which has been shown to be sensitive to irradiation. Using a rabbit model we have undertaken a study to investigate the effect of irradiation on the bony ingrowth on porous coated implants. Forty-five rabbits had porous coated implants surgically placed in the tibiae bilaterally. Each rabbit had one tibae randomly irradiated with 1,000 cGy in 5 fractions starting on the first post-operative day. Animals were sacrificed weekly starting 2 weeks post-operatively and the tibae were sent for pullout studies. The amount of force necessary to pullout the treated tibae was statistically less than the amount of force necessary to remove the untreated tibae at 2 weeks. From 3 weeks on there was no difference in the force necessary to remove the prosthesis from the untreated or treated tibae. Histologically, the untreated tibae showed bone formation while the treated tibae did not. Because of these results, it is suggested that the treatment of patients at risk for development of heterotopic bone be modified to only include the area between the femur and pelvis avoiding treatment of the prosthetic device.
Animals↗
Selective ECG synchronised suction and retroinfusion of coronary veins: first results of studies in acute myocardial ischaemia in dogs.
STUDY OBJECTIVE: The aim of the study was to test an intermittent ECG synchronised suction device which was added to a coronary vein retroinfusion system (selective suction and retroinfusion = SSR) in order to transport oxygenated fluid more efficiently into ischaemic myocardium. DESIGN: The suction period preceding the retrograde pumping period was sufficient to allow the coronary veins to empty upstream of the retroinfusion catheter tip, thus facilitating the refilling of the veins by the retrogradely pumped oxygenated fluid. Subepicardial oxygen partial pressure measurements and determination of post mortem infarct size were used to study the efficacy of SSR treatment in an open chest infarct model. SUBJECTS: 15 beagle dogs were subjected to occlusion of the left anterior descending coronary artery for up to 5 h. MEASUREMENTS AND MAIN RESULTS: Using oxygenated Ringer lactate solution for SSR treatment (given 30 min to 5 h after occlusion of the left anterior descending artery), mean subepicardial PO2 in the ischaemic myocardium of SSR treated dogs increased by 7-12 mm Hg. Mean infarct size was reduced to 5.6(SD 3)% of left ventricle in SSR treated dogs (n = 4) compared to 27(14)% in controls (n = 4). Expressed as percent of volume at risk, mean infarct size was reduced by 84% in SSR treated dogs. CONCLUSIONS: These data suggest that intermittent suction increased the efficacy of coronary venous retroinfusion in acute myocardial ischaemia.
Animals↗
Inhibition of sensory responses of cat inferior olive neurons produced by stimulation of red nucleus.
1. The sensory responsiveness of cells in the inferior olive is known to be suppressed during certain phases of active movement. These experiments were designed to test the possibility that activity in the rubrospinal pathway contributes to this suppression. We recorded from cells sensitive to light touch located in one of the divisions of the inferior olive, the rostral dorsal accessory olive (rDAO), in cats anesthetized with pentobarbitol sodium. Responsiveness to peripheral stimuli was tested during and after trains of conditioning stimuli delivered to the rubrospinal pathway. 2. All 44 cells in our sample of rDAO neurons showed an inhibition of responsiveness to peripheral stimuli after conditioning stimulation of the rubrospinal pathway. Typical conditioning trains consisted of 0.2-ms pulses at 200 Hz for 100 ms. The mean current required for a reduction in firing probability to 0.5 was 31 microA. Slight increases in intensity often completely inhibited responses to peripheral stimuli. 3. Inhibition of responsiveness showed a delayed time course. Peak inhibition occurred approximately 50 ms after the last pulse in the conditioning train. In many cases there was no demonstrable inhibition during the conditioning train. Increases of train frequency, train duration, or stimulus intensity produced stronger and broader periods of olivary inhibition. 4. The lowest threshold points for eliciting rDAO inhibition coincided with either the magnocellular red nucleus (RNm) or the rubrospinal tract (RST). Stimulation at RST sites produced inhibition of responses in the contralateral but not in the ipsilateral rDAO. Transection of the RST in the upper brain stem blocked the inhibition produced by red-nucleus stimulation without altering the inhibition produced by tract stimulation caudal to the transection. The inhibitory effects thus appear to be caused by activation of the rubrospinal pathway. 5. The inhibitory timing observed in this study may be appropriate for explaining the suppression of olivary responsiveness to contact that has been observed in awake animals. Bursts of movement-related, red nucleus discharge often cease approximately 50 ms before the end of movement. This timing would allow peak inhibition to develop at approximately the time of contact with an object at the end of a goal-directed limb movement.
Animals↗
Erythropoietin production in the isolated perfused kidney.
In order to further investigate the dependency of the production of erythropoietin (Epo) on the renal O2 supply, experiments were carried out in the isolated perfused rat kidney (IPRK). The kidneys were perfused with a substrate enriched Krebs-Henseleit solution containing 60 g/l bovine serum albumin at a constant perfusion pressure of 100 mmHg. When the kidneys were perfused at an arterial pO2 of 720 or 150 mmHg (hematocrit 5%), Epo production measured by RIA was very low (0.1-0.2 U/g kidney after 3 h of perfusion). At a pO2 of 20 mmHg, Epo production increased markedly up to 0.9 U/g kidney. However, the production of Epo was little affected by changes in the hematocrit of the perfusion medium from zero to 40%, even if severe anemia was mimicked. These results indicate that Epo production in the IPRK is mainly under the control of the arterial pO2.
Anemia↗
O2-supply to the kidneys and the production of erythropoietin.
The concentration of erythropoietin (Ep) in blood increases little following a reduction of the renal blood flow (rbf). In the present study we examined whether a reduction of rbf in rats induces a lowering of the renal venous PO2. In addition, the combined effects of reduced rbf and hypobaric hypoxia on the production of Ep were studied. To lower rbf, silver clips with stepwisely reduced inner diameters were applied on both renal arteries. The PO2 of renal venous blood decreased gradually to values below 10 mm Hg, when rbf was reduced from 80 to 10% of normal. Under these conditions plasma Ep increased only moderately from 20 +/- 6 to 69 +/- 24 mU/ml within 18-20 h. However, plasma Ep of rats exposed to hypobaric hypoxia (stimulated altitude of 6000 m for 18-20 h) was 431 +/- 68 mU/ml, when rbf was 100-80% of normal, compared to 931 +/- 91 mU/ml, when rbf was reduced to 40-10%. Thus, a reduction of the blood flow to the kidney appears to be no major stimulus for the production of Ep, even when the PO2 in the kidney becomes very low. However, plasma levels of Ep increase markedly, when the whole body O2 offer is lowered. These results support the view that Ep production is not only dependent on the PO2 in the kidney but also under the control of extrarenal O2 sensitive mechanisms. For example, the hypothalamic-hypophyseal system is thought to influence the production of Ep.
Animals↗
Erythropoietin and blood pressure.
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Angiotensin II↗
Isolates of human immunodeficiency virus type 1 from the brain may constitute a special group of the AIDS virus.
The biologic, serologic, and molecular properties of isolates of human immunodeficiency virus type 1 (HIV-1) from the central nervous system (CNS) were determined and compared to those of isolates from peripheral blood and lymph nodes. Among these were pairs of CNS and blood isolates obtained from six infected individuals. The data show that HIV-1 isolates from the CNS can be distinguished from peripheral blood isolates by their (i) relative inability to infect established T-cell lines, (ii) reduced cytopathogenicity, (iii) inability to modulate CD4 antigen expression on infected cells, (iv) efficient replication in peripheral blood macrophages, and (v) insensitivity to serum neutralization. Paired CNS and peripheral blood isolates from the same individual also display some differences in cellular tropism. The blood isolates replicate better in T-cell lines and glioma cell lines, whereas the paired CNS isolates replicate more efficiently in primary macrophages. These results suggest that viruses isolated from the CNS of infected individuals may represent a specific HIV-1 subgroup.
Acquired Immunodeficiency Syndrome↗
Alcohol and drug abuse in the workplace in broad perspective.
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Alcoholism↗
[The use of endorectal sonography for the preoperative staging of rectal tumors].
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Humans↗
A comparison of the effects of renal artery constriction and anemia on the production of erythropoietin.
It is generally assumed that the O2 supply to the kidneys is the major determinant of the synthesis of erythropoietin (Ep). In the present study, the O2 supply of the kidneys of rats was lowered by the reduction of renal blood flow (rbf). Plasma Ep was determined after about 18 h of bilateral application of Goldblatt clips with graded inner diameters. The results were compared to findings in anemic rats, in which the systemic O2 supply was lowered by exchange transfusion of blood with plasma. We found a linear correlation between Ep levels in plasma and the degree of reduction of rbf. However, there was an exponential relationship between Ep levels and the concentration of hemoglobin in blood. In addition, the elevation of plasma Ep was only moderate, when rbf was reduced (maximum 0.07 IU Ep/ml plasma). The increase in Ep concentration was much more pronounced in anemia (up to about 7 IU Ep/ml plasma). From these results it may be concluded that decreasing oxygen supply to the kidney through reduction in renal blood flow (ischemic hypoxia) is less effective in increasing erythropoietin production than reducing the hemoglobin concentration (anemic hypoxia). The possibility must be considered that the increase in renal production of erythropoietin due to anemic hypoxia is triggered by one or more extrarenal signals.
Anemia↗
Complexity of myosin species in the avian posterior latissimus dorsi muscle.
The myosin content of the avian posterior latissimus dorsi muscle, a small fast-twitch muscle similar in fibre type to the much-studied pectoralis major muscle (type IIB), has been explored using high resolution chromatography of the proteolytic fragment known as subfragment-1 and of the products of its limited tryptic digestion, followed by N-terminal sequencing of selected peptides. The complexity of species found greatly exceeds that anticipated from the fibre-type homogeneity of the muscle and from previous studies (Bandman et al., Cell 29 (1982) 645-50; Lowey et al., J. Musc. Res. Cell Motility 4 (1983) 695-716; Crow & Stockdale Dev. Biol. 118 (1986) 333-42). A minimum of four heavy chain species were identified. One form, approximately 40% of the heavy chain complement, appears to be identical to the well-characterized type IIB isoform of the pectoralis major muscle. The remaining species differ from the pectoralis major form in primary sequence. None is identical to the post-hatch isoform of the pectoralis major muscle.
Amino Acid Sequence↗
The changing face of cardiac transplantation: the Washington University Program, 1985-1987.
Since January, 1985, 59 patients have undergone 62 heart transplantations at Washington University School of Medicine. The experience in this program serves as a useful microcosm of the field of cardiac transplantation as a whole to demonstrate certain trends that are becoming evident. Of the patients, 47% had coronary artery disease compared with 40% with cardiomyopathy. Fourteen patients (24%) were 55 years old or older at the time of transplantation. Sixteen patients (27%) required mechanical support of respiration or circulation or both prior to transplantation. Six patients were maintained with a left ventricular or biventricular assist device, and all survived; 1 patient received extracorporeal membrane oxygenation and lived; 7 patients were maintained with an intraaortic balloon pump, 6 of whom survived; and 2 were maintained with a mechanical ventilator and survived. The preoperative waiting period averaged 51 days for the group as a whole. Status-3 patients experienced an average 81-day waiting period, and those in blood group O waited 155 days. In contrast, critically ill patients (status 0) underwent transplantation within an average of 9 days. Actuarial survival at 12 months for all patients, operative survivors, patients age 55 years old or more, and patients bridged to transplantation was 87%, 92%, 84%, and 87%, respectively. Utilizing the combination therapy of cyclosporine, azathioprine, and prednisone introduced by one of us in 1983 and administered to all patients in this series, 50% of patients were rejection free and 56% were infection free at 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Academic Medical Centers↗
Myosin isoforms in normal and dystrophic chickens.
The myosin isoform content in the affected fibers of chickens with inherited muscular dystrophy has been investigated with a new high-performance liquid chromatographic procedure for separation of the tryptic fragments of myosin subfragment 1 (S-1). The results indicate that dystrophic muscle contains substantial amounts of normal adult myosin, together with various myosin species present in normal 5-day posthatch chickens. Confirmation was obtained by comparative peptide mapping of the S-1 tryptic fragments and by N-terminal sequencing of 20-kDa species. Together with data on other contractile proteins and certain metabolic enzymes [Obinata, T., Takano-Ohmura, H., & Matsuda, R. (1980) FEBS Lett. 120, 195-198; Mikasa, T., Takeda, S., Shimizu, T., & Kitaura, T. (1981) J. Biochem. (Tokyo) 89, 1951-1962; Feit, H., & Domke, R. (1982) Cell Motil. 2, 309-315; Cosmos, E. (1966) Dev. Biol. 13, 163-181; Cosmos, E., & Butler, J. (1967) in Exploratory Concepts in Muscular Dystrophy and Related Disorders (Milhorat, A. R., Ed.) pp 197-204, Excerpta Medica, Amsterdam], the results are consistent with the hypothesis that there is a general defect in muscle maturation in avian dystrophy.
Aging↗