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Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 793 records · Page 44Linked to original sources
PubMed1988

Ineffectiveness of adoptive chemoimmunotherapy with lymphokine-activated killer cells, interleukin-2, and cyclophosphamide on palpable intradermal murine bladder cancer.

The effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells and human recombinant interleukin 2 (IL2), on palpable intradermal (i.d.) bladder tumor were studied. The murine transitional cell carcinoma MBT-2 was used in C3H mice. IL2 was given intraperitoneally at 5,000 U/injection three times a day for 5 consecutive days beginning on day 10. LAK cells were generated in vitro from normal splenocytes: 10(7)-10(8) LAK cells were transferred intravenously on day 10 and, in some experiments, also on day 13. IL2 alone, LAK cells alone (total 8 x 10(7], and both in combination showed little or no influence on intradermally growing MBT-2 tumors. Cyclophosphamide was also combined with adoptive immunotherapy (IL2 and LAK). CY (100 mg/kg, i.p. on day 9 or 10) alone was able to suppress i.d. MBT-2 growth significantly. The combination treatment of IL2 and LAK cells with CY caused additional tumor growth suppression in a manner dependent on the total number of LAK cells transferred. The amount of the additional tumor growth suppression was, however, relatively small when compared with CY plus IL2-treated groups. In comparison, experimentally induced 3-day and 10-day pulmonary metastases of MBT-2 cells were treated by the same protocol of IL2 and LAK cells but without CY. IL2 alone reduced the number of gross metastatic nodules in the lung. The addition of LAK cells to the IL2 almost entirely eradicated the 3-day metastatic nodules but was less effective against the 10-day metastases. The data suggest that adoptive immunotherapy with IL2 and LAK cells mediates tumor regression of micrometastases at a selected organ (lung), but is ineffective against the same tumor growing in the skin or in gross metastatic nodules. Host immune suppression by CY was not beneficial in this model in creating a successful therapeutic effect of LAK cells and IL2.

Animals↗
PubMed1988

Eradication of palpable intradermal murine bladder tumors by systemic interleukin-2 and cyclophosphamide in C3H mice.

The effect of cyclophosphamide on interleukin-2 (IL-2) therapy was investigated using the intradermal MBT-2 tumor in C3H mice. Human recombinant IL-2 (Biogen) was given intraperitoneally at doses ranging from 5,000 to 30,000 U, three times a day for 5 or 11-13 consecutive days beginning on day 10 after tumor implantation. When IL 2 was given alone, mice could not tolerate greater than 5 days of 5,000 U IL 2/injection: Administration of 10,000 and 15,000 U/injection of IL-2 for 5 days resulted in 64% (9 of 14) and 100% (14 of 14) mortality, respectively. Chemotherapeutic agents (cisplatin at 6 mg/kg or JM-8 75 mg/kg) and daily administration of cortisone acetate (75 mg/kg) partially protected mice from IL-2-induced toxic deaths. Coadministration of mannitol showed no protective effect. The combination of IL-2 and CY at 75 or 100 mg/kg, however, dramatically reduced the mortality induced by IL-2 and made it possible to escalate the dose and long-term administration of IL-2. Combination administration of 75 mg/kg CY with 15,000 U/injection of IL-2 for 11-13 days caused tumor regressions and resulted in a 66% (8 of 12) cure rate.

Animals↗
PubMed1988

Wavelength dependence for human redoxy-endonuclease-mediated DNA cleavage at sites of UV-induced photoproducts.

Redoxy-endonuclease, an enzyme present in human and other cells, recognizes monobasic photoproducts that occur primarily at sites of cytosine following UV-irradiation of DNA at 254 nm. The wavelength dependence for formation of these photoproducts was determined using end-labeled DNA fragments of defined sequence irradiated with monochromatic light ranging from 254-360 nm as substrates for redoxy-endonuclease partially purified from HeLa cells. The base specificity and extent of DNA cleavage were determined by analysis of the enzyme-generated DNA scission products on DNA sequencing gels. Maximal incision at sites of cytosine and thymine was observed at 280 nm, suggesting that these photoproducts may be relevant with respect to the biological effects of solar radiation.

DNA↗
PubMed1987

Thymine glycol-DNA glycosylase/AP endonuclease of CEM-C1 lymphoblasts: a human analog of Escherichia coli endonuclease III.

A thymine glycol-DNA glycosylase/AP endonuclease has been identified in human CEM-C1 lymphoblasts. The enzyme is active in the absence of divalent cations and has an apparent molecular size of approximately 60,000 daltons. The enzyme releases thymine glycol from osmium tetroxide-damaged DNA via an N-glycosylase activity and is associated with an endonuclease activity that mediates phosphodiester bond cleavage at sites of thymine glycol and apurinic sites. We propose that this enzyme, which we call redoxyendonuclease, is the human analog of a bacterial enzyme, E. coli endonuclease III, that recognizes oxidative DNA damage.

Cations, Divalent↗
PubMed1987

Efficacy of antitumor chemotherapy in C3H mice enhanced by the antiangiogenesis steroid, cortisone acetate.

The effect of "antiangiogenesis" therapy using cortisone acetate (CA) with or without heparin on tumor growth as well as in combination with chemotherapy was investigated. C3H mice were implanted intradermally with N-[4-(5-nitro-2-furyl)-thiazolyl]formamide induced undifferentiated transitional cell carcinoma, MBT-2, in the right flank. The treatment was initiated 9 to 10 days after tumor inoculation. Daily injections of CA (250 mg/kg s.c.) suppressed tumor growth significantly in a dose dependent fashion. Administration of heparin (Elkins-Sinn) at the concentration of 200, 400, or 1000 units/ml in drinking water for 3 to 6 days was neither additive nor detrimental to the effect of CA. Chemotherapy was combined with CA; 3 days of administration of 250 mg/kg of CA in tapering doses was used. The chemotherapeutic agent was injected once 24 h before the initial CA. Combinations of chemotherapy (Adriamycin, 2.5-7.5 mg/kg i.v; cisplatin, 3-9 mg/kg i.p.; cyclophosphamide, 50-150 mg/kg i.p.; cis-(diammino)(1,1-cyclobutanedicarboxylate)platinum(II) (JM-8), 60-150 mg/kg i.p.; mitomycin C, 3-4.5 mg/kg i.p.) with CA showed additive suppression of tumor growth. Mice tolerated chemotherapy alone, CA alone, and both in combination. CA combined with JM-8 was not tolerated. Mice tolerated 100 to 150 mg/kg of JM-8, whereas the addition of CA to JM-8 resulted in a 66% (6 of 9) to 89% (8 of 9) mortality rate. CA at a concentration of 5 and 25 micrograms/ml showed no direct cytotoxic activity against MBT-2 cells in vitro. However, 3 days of administration of 250 mg/kg of CA inhibited tumor angiogenesis generated by MBT-2 cells in C3H mice using a dorsal air sac assay. The data suggest that CA alone inhibits tumor angiogenesis in C3H mice and that antiangiogenesis therapy enhances the antitumor efficacy of chemotherapeutic agents without increasing host toxicity (except for JM-8).

Animals↗
PubMed1987

Central versus peripheral mediation of responses to adenosine receptor agonists: evidence against a central mode of action.

Although adenosine and its analogs have potent effects on the peripheral and central nervous systems, the actions of systemically administered adenosine analogs on the central nervous system are poorly understood. We have previously shown that adenosine analogs depress hippocampal-evoked responses (fEPSPs) in a brain slice preparation, and in the present study, we observed that local pressure ejection of adenosine or R-phenylisopropyladenosine (R-PIA) also reduced the fEPSP recorded in situ in a theophylline-reversible manner. However, systemic administration of R-PIA in up to 1000 times the behaviorally active dose failed to attenuate the fEPSP amplitude. Similar observations were made with systemic injections of 2-chloroadenosine and N-ethylcarboxamidoadenosine, both of which are active in behavioral studies following intraperitoneal or intracerebroventricular injection. Autoradiography showed systemically injected [3H]PIA did not enter the brain in significant concentrations, and this observation was confirmed using microdialysis brain perfusion. These results suggest that systemically administered adenosine analogs do not affect synaptic neurotransmission in the hippocampus because they fail to reach the appropriate receptors.

2-Chloroadenosine↗
PubMed1987

Reciprocal effects of epidermal growth factor and transforming growth factor beta on the anchorage-dependent and -independent growth of A431 epidermoid carcinoma cells.

The effects of epidermal growth factor (EGF) and transforming growth factor beta (TGF beta) on the growth of A431 epidermoid carcinoma cells were studied. Whereas the monolayer growth of A431 cells was inhibited by EGF, it was stimulated by TGF beta. Contrary to the effects on the monolayer growth, EGF stimulated the soft agar growth of A431 cells. The stimulatory effects of TGF beta on the anchorage-dependent growth were antagonized by EGF and those of EGF on anchorage-independent growth were antagonized by TGF beta. These results suggest that both factors not only convey the proliferative signals to A431 cells but also induce phenotypic changes, resulting in a preference for either anchorage-dependent or anchorage-independent growth. Moreover, as the stimulatory effects of EGF on the soft agar growth of A431 cells paralleled its reported stimulatory effects on their in vivo growth, it is also suggested that in vivo responses of cells to certain growth factors may correlate better with their responses in soft agar culture than with those in monolayer culture.

Agar↗
PubMed1987

Relationship between testicular volume and presence of varicocele. A comparative study.

The varicocele, present in many of the male partners of infertile couples continues to generate controversy, particularly as related to its diagnosis and pathophysiology. The purpose of our study was to determine the relationship between testicular volume and the presence or absence of a varicocele. Testicular volume was determined by the use of an orchiometer; the presence of a varicocele was determined by palpation during a Valsalva maneuver. The patients utilized in the study were those seen in our Andrology and General Urology Clinics; 291 patients with varicoceles and 83 control patients (no evidence of varicocele) were used. The left (mean = 21.4 mL) and right (mean = 23.4 mL) testicular volumes of patients with a varicocele were significantly reduced compared with that of the control group (left, mean = 23.4 mL; right, mean = 26.2 mL; p = 0.0041 and p = 0.002, respectively). The testicular volume corrected on the basis of the body mass (V/m2) also was significantly reduced in the varicocele group compared with controls (left p = 0.007; right p = 0.001). Reduced testicular volume relative to body size may be detected prior to actual demonstration of the stress pattern and the presence of a varicocele, and may be useful in early diagnosis. It is suggested that measurement of testicular volume may be a useful adjunct to routine examination of the infertile male.

Adult↗
PubMed1987

Mineral balance in adult men: effect of four refined fibers.

Eleven men consumed a basal diet alone and with cellulose (Na-carboxymethylcellulose, locust bean gum, or karaya gum) added at 7.5 g fiber per 1000 calories for 4 wk each. Food, urine, and fecal composites were collected during the last 8 d of each feeding period. Bowel transit time was not significantly affected; however, total dry fecal weight was significantly increased after the refined fibers compared with that after the basal diet. Adding refined fibers to the basal diet did not significantly affect apparent mineral balance of calcium, magnesium, manganese, iron, copper, or zinc, with the exception of a negative mineral balance for manganese with carboxymethylcellulose. Karaya gum had a mean positive balance for all minerals tested. These results indicate that the hypocholesterolemic effect of the fibers that form gels occurs without compromising mineral balance in those subjects consuming Recommended Dietary Allowance levels of the minerals studied.

Adult↗
PubMed1987

Determination of serotonin turnover in the rat brain using 6-fluorotryptophan.

After intraperitoneal injection of rats with 6-fluorotryptophan (6-FT), brain 5-hydroxytryptamine (5-HT) levels decreased exponentially over 1 h. Depletion was dose-dependent and maximum depletion was observed at 200 mg/kg. 6-FT (200 mg/kg) did not significantly alter the content of 5-hydroxyindoleacetic acid. Turnover rates of 5-HT obtained by the 6-FT and other methods were fairly consistent. 6-FT had little effect on the content of noradrenaline and dopamine. These data suggest that 6-FT completely inhibits tryptophan hydroxylase, in vivo, without affecting the release of 5-HT from 5-HT neurons and with little effect on the activities of tyrosine hydroxylase. Therefore, 6-FT is a good pharmacological tool for studying the turnover rate of 5-HT in the brain.

Animals↗
PubMed1987

Liver toxicity encountered in the Veterans Administration trial of disulfiram in alcoholics.

Alcoholic subjects (453) were randomly assigned to disulfiram or placebo therapy and followed for up to 12 months for drinking. Drinking status was determined from interviews of the subject and a household contact each 2 months and from the analysis of eight blood samples or 39 urines submitted at intervals during the year. Liver status was monitored each 2 months by obtaining serum alkaline phosphatase, bilirubin, and AST. Sensitive criteria were arbitrarily selected to identify about 1/5 of the patients with episodic elevations of liver tests. There was no relationship of liver test elevations to disulfiram treatment. However, the elevated AST related significantly to drinking status (p = 0.004) as did elevated bilirubin (p = 0.044), but not elevated alkaline phosphatase (p = 0.146). Two hundred one patients had liver test elevations at least one time and were continued on drug, four were dropped. One hundred seventy-nine of these patients were drinking, 22 were abstinent, and four were indeterminant. It is concluded that patients on disulfiram with minor liver test abnormalities are usually drinking.

Alcoholism↗
PubMed1987

Aortic ejection fraction: a new hemodynamic parameter and its relationship to aortic insufficiency.

Pulsations of the ascending aorta during fluoroscopy in patients with aortic insufficiency (AI) have been described. The authors present their observations of a similar phenomenon in patients who have AI undergoing scintiangiography. In addition, this paper describes a technique to validate and quantitate this finding. They studied 17 patients with documented AI and 14 subjects of a control group. First-pass studies were acquired in the RAO 15 degrees projection. Regions of interest were placed over the proximal aorta during systole and diastole. An aortic ejection fraction (AF) was determined. The calculated AEF data were correlated with the presence or absence of AI. The mean AEF from the 17 AI patients was 27.1 +/- 7.2%, while the mean for the non-AI group was 12.0 +/- 6.5% with p less than .001. An AEF of 18% separates the two groups with a sensitivity, specificity, and accuracy of 88%, 86%, and 87% respectively. Preliminary data demonstrate a mean reduction in AEF of 12.2 percentage points in 7 AI patients who underwent aortic valve replacement. The AEF may be a useful new parameter to evaluate hemodynamic changes associated with aortic valve replacement in patients with aortic insufficiency.

Adult↗
PubMed1987

Disseminated neonatal herpes simplex virus infection with necrotizing encephalitis--an autopsy case.

An autopsy case of disseminated HSV type 2 infection occurring in a neonate at 32 weeks' gestation, delivered by cesarean section after premature rupture of membrane of 7 days duration, is presented. Herpes simplex virus type 2 was isolated from the vesicular skin lesion. The mother and patient had specific antibody to type 2 herpes simplex virus. Patient's parents had denied any herpetic orolabial or genital lesion during or before this pregnancy. Cultures from the cervical and vaginal swabs of the mother were negative for HSV. Postmortem examination showed hepatic necrosis, skin vesicle, devastating necrotizing inflammation of the brain, chorioretinitis and interstitial pneumonitis.

Autopsy↗