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Biomedical subjects

K E Lee

Publications and source records attributed to K E Lee.

At least 19 recordsLinked to original sources
PubMed1992

Allotransplantation of rat islets into the cisterna magna of streptozotocin-induced diabetic rats.

Islets were isolated from the pancreata of Sprague-Dawley rats and transplanted into streptozotocin-induced diabetic outbred Wistar rats. The effect of transplantation of islets into the cisterna magna on the diabetic state of the recipients was compared with that of the conventional transplantation of islets into liver via the portal vein. After successful intraportal (IP) transplantation, rejection took place between days 7 and 15 in all diabetic recipients. All of the eleven rats surviving after stereotaxic implantation of islets into the cisterna magna returned to normoglycemia within 7 days after transplantation. Nine of the recipients with intra-cisterna magna (IM) islet allografts were still normoglycemic at 210 days after transplantation. The glucose disappearance rate of the IM transplant rats was slower than that of the IP transplant rats, and blood glucose returned to the normal basal level within 5 hr following glucose administration. Although the insulin levels were almost undetectable in cerebrospinal fluid before IM transplantation, the insulin levels were markedly increased after IM transplantation and twice as great in CSF than blood. Thus, these findings indicate that the cisterna magna can serve as an immunologically privileged site for implantation of allogeneic pancreatic islets, and islets in CSF can regulate and maintain normal glucose homeostasis via secretion of insulin across the blood-brain barrier.

Animals↗
PubMed1992

Comparison of six microcomputer dietary analysis systems with the USDA Nutrient Data Base for Standard Reference.

We compared the general operating features and nutrient databases of six microcomputer dietary analysis systems. A 3-day food record with 73 food items was entered into each program; nutrient averages were compared with the US Department of Agriculture Nutrient Data Base for Standard Reference (USDA NDB), full version, release 9, for microcomputers. The six programs were found to vary widely in cost, number of foods and nutrients in the database, use of non-USDA data and imputation of data for missing values, number of print/export options, time to analyze the 3-day food record, and overall ease of use. Although all of the microcomputer dietary analysis systems were within 7% of the USDA NDB for energy, protein, total fat, and total carbohydrates, the proportion of other nutrients varying more than 15% from the USDA NDB varied considerably between programs. Variance among programs for 3-day food record nutrient values occurred because of differences in the number of food items included in the database (leading to varying degrees of substitution), the recency of the nutrient data (whether or not the most recent USDA releases had been incorporated), and the number of missing values (the degree to which non-USDA sources or estimated calculations were used to fill in the blanks from the USDA standard). Our results demonstrate that it is important for each dietitian to carefully choose a microcomputer dietary analysis system that is suitable to specific and predetermined needs.

Databases, Factual↗
PubMed1992

[Comparison between clinical response and in vitro chemosensitivity of solid tumors in the succinic dehydrogenase inhibition test].

We describe our experience with succinic dehydrogenase inhibition (SDI) test for solid tumors as a chemosensitivity test using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. Specimens were obtained from 76 surgical resected tumors, including 32 colon cancers, 24 stomach cancers and 16 lung cancers. Following enzymatic dissociation of scissors-minced tumors, viable cells were cultured in serum free medium (S-Clone SF-B) for 4 days with eight drug concentrations obtained by 2-fold dilution of drugs. Among 76 specimens tested, 48 specimens including 15 colon cancers, 18 stomach cancers and 15 lung cancers were successfully evaluated. For the purpose of judgement, 50% inhibitory concentration (IC50) was calculated in each case. Tumor specimen was regarded as sensitive to a given agent when the IC50 value was the same or smaller than the cut-off concentrations (1 microgram/ml for mitomycin C, 5 micrograms/ml for cisplatin, 2 micrograms/ml for adriamycin and 50 micrograms/ml for 5-fluorouracil), and was regarded as resistant when it was larger than these levels. In vitro vs in vivo drug sensitivity was successfully evaluated in 23 cases. The overall predicting accuracy rate was 78% (18/23), with one true positive, 5 false positive and 17 true negative cases. This test appeared to be useful to tailor effective agents for patients because of its relatively high successful and predictive rates.

Adult↗
PubMed1990

Cortisone inhibition of tumor angiogenesis measured by a quantitative colorimetric assay in mice.

A simple and quantitative angiogenesis assay was developed. Using this assay, the angiostatic effect of cortisone acetate (CA) on three murine tumors was studied. Tumor cells were inoculated i.d. into the syngeneic or heterogeneic hosts (day 0) and the degree of angiogenesis was quantitated on day 3 by measuring the tumor vascular volumes using an Evan's blue perfusion technique. CA treatment (250 mg/kg for 3 days) significantly suppressed tumor angiogenesis; however, the degree of angiostatic effect was influenced by the tumor types and by the mouse strain used. MBT-2 bladder cancer angiogenesis was suppressed by 77%-80% of controls in C3H/HeN and C57B1/6 mice, whereas MBT-2 angiogenesis in BALB/c mice was significantly less suppressed by CA (65% inhibition) as compared with values obtained for C3H mice. B16 melanoma or Line-1 lung-cell carcinoma-induced angiogenesis was suppressed by 57%-66% in their syngeneic or heterogeneic hosts. The combined administration of CA and heparin (Sigma; 1,000 units/ml in drinking water) did not influence the outcomes. The data suggest that host factor(s) and tumor factor(s) influenced the expression of CA angiostatic activity. This colorimetric assay enabled a quantitative estimation of the degree of angiogenesis in mammalian animals.

Animals↗
PubMed1990

Influence of high-energy shock waves and cisplatin on antitumor effect in murine bladder cancer.

The potential application of high-energy shock waves (HESW) for control of experimental bladder cancer was investigated. Subcutaneous 3-d murine bladder cancer (MBT-2) in C3H mice were exposed to HESW alone (250 to 1,500 shocks) or in combination with cisplatin (5 to 10 mg/kg, i.p.). Although HESW alone showed no influence on tumor growth, HESW/cisplatin combination therapy suppressed tumor growth more than cisplatin alone. Subsequent studies revealed that an air-fluid interface relative to tumor location played a pivotal role for the chemosensitizing effect of HESW. HESW treatment was able to enhance the cisplatin cytotoxicity only when the tumors were placed adjacent to the air-fluid interface.

Animals↗
PubMed1989

Improved use of buthionine sulfoximine to prevent cisplatin nephrotoxicity in rats.

Male Sprague Dawley rats were treated with buthionine sulfoximine (BSO) and cisplatin in different doses and schedules to optimize the chemoprotective effect of BSO against cisplatin nephrotoxicity. BSO at 4 mmol/kg, administered s.c. 2 h prior to cisplatin, resulted in normal blood urea nitrogen (BUN) levels in rats treated with 3 or 4 mg/kg cisplatin, and modestly, but significantly reduced the toxicity of cisplatin at 5 mg/kg. Administration of BSO (4 mmol/kg) at intervals ranging from 0 to 16 h prior to cisplatin (5 mg/kg) resulted in a significant reduction in BUN values. A BSO dose as low as 0.04 mmol/kg was found to be as effective as 4 mmol/kg against nephrotoxicity associated with cisplatin at 4 mg/kg. Repetitive injections of BSO (1 mmol/kg every 12 h, four times, beginning 2 h prior to cisplatin) significantly inhibited elevations of BUN associated with higher-dose cisplatin (6 mg/kg), whereas a single BSO injection of 4 mmol/kg was ineffective. The degree and duration of renal glutathione depletion was related to the dose of BSO. Renal glutathione content following 4 mmol/kg BSO was 38% of control at 2 h and 40% at 24 h; following 0.04 mg/kg, glutathione was 47% at 2 h and almost 100% at 24 h. Simultaneous in vitro administration of BSO did not inactivate cisplatin cytotoxicity as measured by the colony-forming ability of MBT-2 cells in soft agar. These data indicate that repeated injections of BSO, beginning prior to cisplatin administration, would improve the nephroprotective effect without compromising the chemotherapeutic efficacy of cisplatin. It is suggested that the ability of BSO to reduce cisplatin nephrotoxicity may not correlate with the degree of renal glutathione depletion and that the mechanism of action is unlikely to involve direct inactivation of cisplatin.

Animals↗
PubMed1989

Effect of systemic glutathione depletion by buthionine sulfoximine on sensitivity of murine bladder cancer to cytotoxic agents.

The effect of systemic glutathione (GSH) depletion on sensitization of bladder cancer cells to various antineoplastic agents was investigated using murine model, MBT-2. Subcutaneous injection(s) of buthionine sulfoximine (BSO) significantly depleted the GSH content in the tumor and organs. BSO pretreatment produced significant enhancement in the antitumor effect of cyclophosphamide (CY), though it failed to sensitize the tumors to doxorubicin hydrochloride (Adriamycin), cisplatin, mitomycin C, JM-8, methotrexate, vinblastine, and tumor necrosis factor. Mice tolerated cytotoxic agents alone and in combination with BSO except for cisplatin in combination with BSO. A 29 percent (4/14) mortality rate was observed in mice treated with BSO and divided schedule of cisplatin.

Animals↗
PubMed1988

Interleukin 2 suppression of a murine bladder cancer implanted into kidney, bladder and skin; its organ specificity.

Little is known about organ associated tumor response to systemic interleukin 2 (IL2) therapy. The effect of IL2 on bladder cancer growth in the skin and in the genitourinary tract was investigated. C3H mice were implanted with the syngeneic transitional cell carcinoma, MBT-2, intradermally (i.d.), beneath the left renal subcapsular area, and in one experiment, simultaneously in the bladder. IL2 (human recombinant form; Biogen Research Co) was given i.p. at 5000 U thrice daily for 5 consecutive days commencing on Day 3, or for 10 to 11 days commencing on Day 10 with some doses omitted at signs of toxicity. For comparison, mice bearing 3-d and 10-d tumors in the skin and subcapsular kidney were treated with chemotherapy (cisplatin, 6 mg./kg. X 3; mitomycin C, 3 mg./kg. X 3; cyclophosphamide, 75 mg./kg. X 1). IL2 therapy mediated growth suppression of 10-d tumors in the genitourinary organs and skin at a similar rate. In contrast to IL2, systemic chemotherapy mediated tumor suppression in an organ specific manner; renal subcapsular tumors responded to the chemotherapy, whereas i.d. tumors were insensitive. Three-day tumors (both i.d. and renal subcapsular tumor) responded relatively well to each treatment compared to 10-d tumors. These data suggest that in systemic immunotherapy with IL2, anatomic location of the tumor is less important for inducing an antitumor response than in chemotherapy.

Animals↗
PubMed1987

Inhibition of cisplatin-induced nephrotoxicity in rats by buthionine sulfoximine, a glutathione synthesis inhibitor.

DL-Buthionine-(S,R)-sulfoximine (BSO), a glutathione-depleting agent, was found to diminish the nephrotoxic effect of cisplatin (cis-diamminedichloroplatinum). Pretreatment of rats with BSO (4 mmol/kg s.c.) 2 h prior to cisplatin, either as a single dose of 5 mg/kg or at a daily dose of 2.5 mg/kg for 3 consecutive days, resulted in diminished elevations of plasma BUN concentration and decreased cisplatin-induced inhibition of renal gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase activity measured 6 days following treatment. Administration of BSO prior to cisplatin at 7.5 mg/kg did not significantly alter the effect of cisplatin on either BUN concentration or enzyme activity. The influence of BSO pretreatment on the antitumor activity of cisplatin was studied using implantation of a murine bladder cancer (MBT-2) in C3H mice. Pretreatment of mice with BSO (5 mmol/kg) did not influence cisplatin antitumor efficacy.

Animals↗
PubMed1987

Effect of intravesical administration of tumor necrosis serum and human recombinant tumor necrosis factor on a murine bladder tumor.

The effect of intravesical administration of tumor necrosis factor (TNF) on the implantability and growth of bladder cancer was studied using the murine tumor model, MBT-2. Crude TNF was prepared from serum (TNS) of BCG infected rats after injection of endotoxin or the recombinant product of human TNF-alpha was used. Treatment was begun 24 hr. or seven days after tumor instillation and repeated three times. Tumor implantability and tumor weight were determined on day 21. Low dose TNF (200 U), given in the form of TNS, failed to suppress the growth of established tumors (seven-day tumor). It did, however, significantly reduce tumor implantability. The growth of seven-day tumors was significantly suppressed by administration of higher dose of TNF (3,700 U) given in recombinant form.

Administration, Intravesical↗
PubMed1987

Reduction of bladder cancer growth in mice treated with intravesical Bacillus Calmette Guerin and systemic interleukin 2.

The effect of systemic administration of Interleukin 2 (IL2) on intravesical Bacillus Calmette-Guerin (BCG) therapy was studied in an established murine bladder tumor, MBT-2. BCG (100 micrograms.) was administered intravesically on days 7 and 14 after seeding bladders with MBT-2 cells. IL2 (5,000 U/injection) was given intraperitoneally every eight hours for 10 times (days seven through 10 and 14 through 17). BCG or IL2 therapy alone failed to reduce incidence of tumor implantation and tumor weight; whereas, combined treatment with BCG and IL2 reduced tumor weight significantly compared to saline or BCG treated mice. Cytotoxicity was assessed in a four-hour 75Semethionine-release assay. Augmentation of natural killer cell activity was only observed in mice treated with BCG plus IL2. MBT-2 target cells were not lysed by spleen cells from mice treated with BCG or saline. IL2 therapy produced lymphokine-activated killer cell activity, though combining BCG with IL2 suppressed this activity after each course of treatment. The results suggest that combined treatment with IL2 enhances the therapeutic effect of BCG therapy. However, this enhancement of antitumor activity is not clearly explained by augmentation of natural killer or in vivo-generated lymphokine-activated killer cells.

Administration, Intravesical↗
PubMed1987

Interferon sequence homology and receptor binding activity of ovine trophoblast antiluteolytic protein.

Sequencing of the 40 N-terminal amino acids of the blastocyst protein responsible for blocking corpus luteum regression in early pregnancy in sheep revealed a 37% homology with human alpha-interferon; 28% of the remaining amino acid changes were conservative. 125I-Labelled human alpha-interferon bound to membrane receptors from sheep uteri with an approximate Kd of 4 x 10(-11) M; binding was inhibited by unlabelled alpha-interferon or purified blastocyst antiluteolytic protein. The blastocyst antiluteolytic protein therefore closely resembles the interferon-alpha family of antiviral proteins.

Amino Acid Sequence↗
PubMed1986

[Effect of metoclopramide on gastric distension and lethal toxicity of cisplatin in mice].

Mice treated with cisplatin (cDDP), were found to have considerably bloated stomachs presumably resulting from paralysis of gastric emptying without appetite suppression and emesis. Repeated administration of metoclopramide (MCP) not only reduced gastric distension, but also the number of toxic deaths after 13 mg/kg of cisplatin i.p. The mechanism of action by which MCP increased the resistance of mice to cDDP seemed to be alleviation of systemic dehydration by means of enhanced gastric emptying.

Animals↗
PubMed1985

Effect of freezing on histologic and biomechanical failure patterns in the rabbit capital femoral growth plate.

Ten pairs of proximal femora were harvested from 8-week-old New Zealand white rabbits. Experimental shear fractures were then created in vitro, and load-displacement curves were recorded. One specimen from each animal was tested within 4 h of death, whereas the contralateral specimen was frozen for 10 to 20 days and thawed prior to testing. Histologic sections of the fractured specimens were studied. No statistically significant differences could be demonstrated between the fresh and the frozen/thawed specimens in either the histologic patterns or the shear load or stress to failure.

Analysis of Variance↗
PubMed1985

Tuberculosis presenting as carpal tunnel syndrome.

A 44-year-old man presented with typical symptoms, signs, and laboratory findings of carpal tunnel syndrome. Mycobacterium tuberculosis was cultured from the flexor tenosynovium excised at surgery. Tuberculosis should be considered in the differential diagnosis of carpal tunnel syndrome with unexplained chronic synovitis. The diagnosis may be missed unless a tissue specimen is analyzed specifically with acid-fast stain and culture. Therapy should include excision of involved synovium, early postoperative mobilization, and appropriate chemotherapy.

Adult↗
PubMed1985

Phosphate excretion and reabsorption in the conscious dog.

When normal conscious dogs were given small doses of (NH4)2HPO4 by stomach tube to increase their plasma PO4, the rate of excretion of PO4 increased without change in creatinine clearance. After eating meat, increased PO4 excretion was accompanied by increase in both creatinine clearance and plasma PO4. The calculated rate of tubular reabsorption of PO4 did not change significantly after (NH4)2HPO4 administration, but there was a significant increase in PO4 reabsorption after meat; in comparison there was no change in SO4 reabsorption. Similarly, administration of certain amino acids, which caused an increase in creatinine clearance, also caused a significant increase in PO4 reabsorption. Administration of SO4 with PO4 had no significant effect on PO4 reabsorption. It appears from the results, that PO4 has an apparent tubular maximum rate of reabsorption (Tm) when plasma PO4 alone is varied; but this Tm is not a real maximum because PO4 reabsorption increases above this value after the administration of meat or amino acids, both of which cause an increase in glomerular filtration rate. There is no evidence to suggest that there is any inhibition of PO4 reabsorption by SO4 or amino acids.

Absorption↗