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Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 811 records · Page 45Linked to original sources
PubMed1990

Prostatic ductal system in rats: regional variation in morphological and functional activities.

The rat prostate is a complex ductal system with branches and subbranches extending from one end to another. Owing to the relative distance of various regions of the duct from the urethra, the entire length of the ductal system can be arbitrarily divided into three segments, i.e., the proximal, intermediate, and distal segments. The present study was carried out to assess the regional variation in cellular activities in this ductal system. Ventral prostates from adult Sprague-Dawley rats were dissected so that an individual ductal system was mechanically isolated and longitudinally sectioned to reveal various segments. Epithelial cells lining distal segments were tall-columnar type and were actively engaging in mitotic activity. Cells in intermediate segments were also tall-columnar type. However, they were mitotically quiescent, but able to produce secretory proteins. Evidence of programmed cell death was not observed in either of these two segments. Cells in proximal segments, on the other hand, were low-columnar or cuboidal in shape and were stained heavily for cathepsin D, a marker associated with late manifestation of cell death. Following castration in adult rats, there was a reversal in the site of programmed death in cells lining the ductal system. By Day 4 post-castration, distal segments contained many epithelial cells with intense cytoplasmic staining for cathepsin D while proximal segments showed a reduction in number of positively stained cells. By Day 7 post-castration, cells in proximal segments, though atrophied, were devoid of staining for cathepsin D.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen-Binding Protein↗
PubMed1990

Immunomagnetic purging of bone marrow: a model for negative cell selection.

Many in vitro techniques have been developed for removing cancer cells from the marrow of patients who are to undergo autologous bone marrow transplantation (ABMT). These purging techniques can be classified as immunological or pharmacological. The immunomagnetic technique has been widely used in neuroblastoma patients. It depends on an interaction between target neuroblastoma cells in the marrow and a complex of specific monoclonal antibodies and magnetized microspheres, the target cells being selectively removed by passage through a magnetic field. Laboratory studies with neuroblastoma and acute lymphoblastic leukemia cells have shown the high efficiency of this technique in selectively removing cancer cells while retaining adequate numbers of normal hematopoietic cells for subsequent reinfusion into the patient. Clinical studies in several hundred neuroblastoma patients, as well as small numbers of acute lymphoblastic leukemia, breast cancer, and myeloma patients, suggest that this is a clinically safe and effective technique. However, no clinical trial has been conducted comparing ABMT with and without in vitro marrow purging. Until such time, we will regard immunomagnetic purging as "standard of care" for neuroblastoma patients receiving ABMT.

Bone Marrow↗
PubMed1990

Characterization of thermoanaerobacter glucose isomerase in relation to saccharidase synthesis and development of single-step processes for sweetener production.

Regulation of glucose isomerase synthesis was studied in Thermoanaerobacter strain B6A, which fermented a wide variety of carbohydrates including glucose, xylose, lactose, starch, and xylan. Glucogenic amylase activities and beta-galactosidase were produced constitutively, whereas the synthesis of glucose isomerase was induced by either xylose or xylan. Production of these saccharidase activities was not significantly repressed by the presence of glucose or 2-deoxyglucose in the growth media. Glucose isomerase production was optimized by controlling the culture pH at 5.5 during xylose fermentation. The apparent temperature and pH optima for these cell-bound saccharidase activities were as follows: glucose isomerase, 80 degrees C, pH 7.0 to 7.5; glucogenic amylase, 70 degrees C, pH 5.0 to 5.5; and beta-galactosidase, 60 degrees C, pH 6.0 to 6.5 Glucose isomerase, glucogenic amylase, and beta-galactosidase were produced in xylose-grown cells that were active and stable at 60 to 70 degrees C and pH 6.0 to 6.5. Under single-step process conditions, these saccharidase activities in whole cells or cell extracts converted starch or lactose directly into fructose mixtures. A total of 96% of initial liquefied starch was converted into a 49:51 mixture of glucose and fructose, whereas 85% of initial lactose was converted into a 40:31:29 mixture of galactose, glucose, and fructose.

Journal Article↗
PubMed1990

Effect of tolazoline on persistent hypoxemia in severe hyaline membrane disease.

Ten critically-ill preterm infants with severe hyaline membrane disease received tolazoline because of persistent hypoxemia refractory to the administration of 100% oxygen and mechanical ventilation. Seven infants (70%) responded immediately with an increase in PaO2 greater than or equal to 20 mmHg in the umbilical arterial gas within 60 minutes after bolus infusion (1 to 2 mg/kg) of tolazoline. Twenty-four hours later after the tolazoline infusion, the FiO2 had been decreased from 1.0 to a mean of 0.82 +/- 0.16, and the MAP from 16.5 +/- 1.8 to 15.6 +/- 4.5 cm H2O. Four of 7 infants (57%) who had an immediate response survived, whereas none survived out of 3 infants who failed to respond initially. Three infants experienced relatively severe complications possibly related to tolazoline. There appears to be a place for the use of tolazoline in a severely hypoxemic infant with hyaline membrane disease who is being ventilated, and in whom arterial oxygenation cannot be improved by a further increase in the inspired oxygen concentration or by an alteration of ventilator settings.

Humans↗
PubMed1990

Immunomagnetic microsphere mediated purging of cALLa positive leukemic cells from bone marrow for autologous reinfusion.

Bone marrow from sixteen patients with cALLa positive ALL have been treated with a monoclonal antibody (MoAb) cocktail which includes DuALL-1 (CD9), WCMH15.14 (CD10) and HD-37 (CD19). Following antibody treatment, marrows were incubated (30 minutes) with anti-murine-IgG1 (Fc) coated magnetic microbeads and passed through a graded magnetic field chamber. Two problems have had to be addressed: (1) More marrow cells must be processed than in marrows from patients with neuroblastoma, for which the separation chamber was originally developed, requiring the use of more beads, causing occlusion of the chamber's collection surface. This has been corrected by using a large surface area pre-magnet for the elimination of excess microbeads prior to processing in the main chamber; (2) Up-modulation (up to 40% positive cells) of the CD9 associated antigen has been detected. To avoid difficulty, marrows are being routinely screened prior to harvest for purging, and purging is delayed for patients with elevated CD9 levels. Eight patients have been reinfused, with no morbidity or mortality associated with the purging or other ex vivo handling of the marrow.

Antibodies, Monoclonal↗
PubMed1990

The 24 h blood pressure responses of hypertensives to a once-a-day cilazapril regimen.

The efficacy of once-a-day cilazapril (a new long acting converting enzyme inhibitor) therapy for the 24 h control of hypertension and its effects on the renin-angiotensin axis were investigated. Twenty-four uncomplicated hypertensive patients whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo were randomly assigned on a double-blind basis to receive either continued placebo or cilazapril therapy at a single dose of 1.25, 2.5 or 5.0 mg/day for a further four weeks. At the end of weeks 4 and 8, systolic and diastolic blood pressures and heart rates were recorded, supine and standing, at 0, 2, 4, 6, 9, 12 and 24 h following a single dose of drug. At the same times, blood was withdrawn for determination of plasma renin activity and aldosterone. Supine and erect systolic and diastolic blood pressures were lowered to normotensive levels with an optimal response being achieved at a dose of 2.5 mg/day. Supine and erect heart rates were unchanged with respect to drug dosage, and the reflex increase in heart rate and diastolic blood pressure on changing from supine to erect posture was maintained in all groups. Maximum antihypertensive efficacy was from 2 to 6 h after drug ingestion. There were no changes in resting aldosterone, but plasma renin activity was increased at all drug dosages. A single 2.5 mg dose of cilazapril provides blood pressure control for a 24 h period. Cilazapril does not appear to interfere with the reflex autonomic responses to postural change.

Adult↗
PubMed1990

Relative efficiency of leukemic cell depletion using anti-murine-IgG1(Fc) or anti-murine-IgG coated immunomagnetic microbeads.

Microbeads for immunomagnetic bone marrow purging, to which sheep anti-mouse-IgG1(Fc) antibodies have been linked, and beads linked with antibodies against whole murine immunoglobulin were compared. Competitive binding studies, in which Fc fragments and Fab fragments were titrated onto the microbeads, followed by incubation with 125I-labeled whole mouse Ig, revealed that the beads linked with anti-mouse-IgG1(Fc) specifically bound the Fc region of the murine immunoglobulin molecules. The total amount of antibody of either IgG1 or IgG2 isotype that would adhere to microbeads linked with either type of antibody, as revealed by secondary binding with 125I rabbit antimouse Ig, was identical, suggesting that similar numbers of antibody binding sites were available. In cell depletion studies, it was found that if IgG1 isotype monoclonal antibodies were employed as binding intermediaries between the target cells and the microbeads, the efficiency of target cell depletion was superior with the anti-mouse-IgG1(Fc)-coated beads, even if the amount of MoAb coating the target cells was suboptimal. However, if the intermediary antibodies were of the IgG2 isotype, the efficiency of target cell depletion with these beads was inferior. These findings indicate that the efficiency of immunomagnetic bone marrow purging is dependent upon matching of the targeting MoAb and the secondary antibodies that link to the surface to the microbeads.

Bone Marrow Transplantation↗
PubMed1990

Transporting bone marrow for in vitro purging before autologous reinfusion.

We describe the procedures employed for transporting bone marrow to and from a central facility. Marrow has been harvested from 80 patients with neuroblastoma, at 16 centers which are geographically dispersed throughout North America. Marrow from the outside transplant centers was packed on wet ice or cold packs in insulated containers, and transported by commercial carriers or chartered aircraft to the central processing laboratory. Post processed marrows were frozen in liquid nitrogen and returned by commercial carrier to the referring institution. In comparing transported with non-transported but similarly treated marrows, no differences were found in any of the following parameters: (1) CFU-GM recovery, (2) fraction viable cells at thawing, or (3) time to engraftment in patients. We conclude the transportation of harvested marrows to a central purging facility is safe. Based on this experience, we propose a set of standards, which, if adhered to, will insure the continued safe processing, shipping, and storage of bone marrow in all centers so engaged.

Bone Marrow Transplantation↗
PubMed1990

Therapeutic efficacy of recombinant tumor necrosis factor alpha in an experimental model of human prostatic carcinoma.

Prostatic carcinoma represents the second leading cause of cancer mortality in men and is responsible for over 25,000 deaths each year. Currently, no curative therapy is available for metastatic carcinoma of the prostate. The present studies were undertaken to assess the efficacy of recombinant tumor necrosis factor alpha (TNF) in the therapy of experimental prostatic carcinoma. TNF was cytotoxic to the prostate cancer cell lines PC3, DU145, and LNCAP but not benign prostatic epithelial and stromal cells in vitro. The sensitivity of the prostatic carcinoma lines to TNF-mediated cytotoxicity was enhanced by the presence of actinomycin D. Intravenous administration of TNF (50-100 micrograms/kg) to nude mice bearing subcutaneous PC3 tumors resulted in significant inhibition of primary tumor growth compared to control. TNF was also effective in reducing the growth of intraabdominal PC3 tumors induced by intrasplenic injection of PC3. Furthermore, the incidence of microscopic PC3 foci in the spleen, liver, lung, and diaphragm was diminished in mice receiving TNF therapy. These studies demonstrate the potential of TNF in the therapy of human prostatic carcinoma.

Animals↗
PubMed1989

Two-dimensional protein profiles of cultured stromal and epithelial cells from hyperplastic human prostate.

Studies were undertaken to compare and contrast the two-dimensional protein profiles of epithelial and stromal cells from hyperplastic human prostate to establish the protein composition of the two major cellular components of the prostate. Epithelial and stromal cells were isolated from human prostate obtained from patients undergoing open prostatectomy for benign prostatic hyperplasia (BPH). Proteins, isolated from the two cell populations and separated by two-dimensional (2D) electrophoresis, were analyzed by silver staining, fluorography of [35S]-methionine-labeled proteins, and immunoprotein blotting. Isolated prostatic epithelial cells, but not stromal cells, contained cytokeratin polypeptides 5, 6, 7, 8, 13, 14, 15, 16, 17, 18, and 19. Although vimentin could not be identified in silver stained 2D gels and fluorographs of cultured prostatic epithelial cells, a low level of immunoreactivity was noted following immunoblot analysis of epithelial cells proteins by the use of an anti-vimentin polyclonal. Vimentin was prominently expressed in cultured prostatic stromal cells and could be identified on silver stained 2D gels, fluorographs, and immunoblots of stroma-derived proteins. In addition, stromal marker proteins SM1, SM2, and SM3 were identified in 2D gels of stromal cells to distinguish them from epithelial cells. These studies demonstrate (1) the two-dimensional protein profile and cytokeratin polypeptide composition of cultured epithelial cells from hyperplastic human prostate and (2) the 2D protein profile of cultured prostatic stromal cells and identification of specific stromal marker proteins.

Cells, Cultured↗
PubMed1989

Intracellular metabolites of cisplatin in the rat kidney.

The appearance of low-molecular-weight metabolites of cisplatin in the cytosol of cells from the cortex and outer medulla of the rat kidney has been examined using HPLC up to 24 h following cisplatin administration. Comparison was made between these metabolites and those present in plasma, urine and liver. The effect of sodium chloride (NaCl) pretreatment, which is known to reduce cisplatin-induced nephrotoxicity, on these metabolites was also investigated. Platinum levels in the kidney cortex and medulla and the cytosol reached maximal levels within 1 h of i.p. injection of 5 mg/kg cisplatin. At least six platinum species, including cisplatin, were present 1 h post-dosing, with the principal species being the parent drug; all of these species were either neutral or negatively charged. Although the concentration of most of the platinum species fell with time, that of one species eluting before cisplatin rose, and by 24 h it was the major metabolite. Cisplatin and two other major cytosolic platinum species were also present in urine and plasma, both of which also contained a number of charged species that were absent from the cytosol. The liver cytosol contained at least five metabolites 1 h post-dosing, but, in contrast to the kidney cytosol at the same time, the predominant species was that eluting before cisplatin and not cisplatin itself. One of the metabolites in the cytosol and urine had the same retention time as an adduct of cisplatin with glutathione and with cysteine. Urinary samples also contained a metabolite coeluting with aquated cisplatin. Pretreatment of animals with NaCl significantly reduced the platinum concentration in the kidney, with a corresponding decrease in the cytosolic metabolites; this may have contributed significantly to the reduction in cisplatin-induced nephrotoxicity after NaCl pretreatment. NaCl also significantly reduced a possible aquated species present in the urine, which may also have contributed to the reduction in nephrotoxicity. The data suggest that cisplatin itself may be the nephrotoxic species, since it is the intracellular platinum compound present in highest concentration during the early critical period after its administration.

Animals↗