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Biomedical subjects

T Kim

Publications and source records attributed to T Kim.

At least 199 records · Page 11Linked to original sources
PubMed1993

The paraventricular nucleus is uniquely responsive to the feeding stimulatory effects of steroid hormones.

The paraventricular nucleus is uniquely responsive to the feeding stimulatory effects of steroid hormones (Tempel, D.L., Kim, T. and Leibowitz, S.F. Brain Research 00: 000-000). This study tested the effects of hypothalamic as well as extrahypothalamic implants of the adrenal steroids, corticosterone (CORT) and aldosterone (ALDO), on food intake and macronutrient selection in sham-operated and adrenalectomized (ADX) rats 1 h after administration. Consistent with a previous experiment, implants of CORT and ALDO in the hypothalamic paraventricular nucleus (PVN) were effective in stimulating food intake. These tests, conducted at the onset of the active feeding cycle, showed PVN implants of CORT to potentiate specifically carbohydrate intake in ADX rats, while having no effect in sham rats. This was in contrast to PVN ALDO which predominantly stimulated fat intake in sham as well as ADX rats. Neither CORT nor ALDO had any effect on food intake after implantation into other hypothalamic or extrahypothalamic sites tested. These unresponsive hypothalamic sites were the dorsomedial and ventromedial nuclei, perifornical lateral hypothalamus, and arcuate nucleus. Extrahypothalamic sites including the dorsal CA1 region of the hippocampus, the central nucleus of the amygdala and the lateral septum were also unresponsive to steroid implants. These results identify the PVN, and the steroid receptors located within it, as having a specific function in mediating the action of CORT and ALDO on carbohydrate and fat intake, respectively.

Adrenalectomy↗
PubMed1993

Simultaneous analysis of 25 pesticides in crops using gas chromatography and their identification by gas chromatography-mass spectrometry.

The simultaneous analysis of 25 pesticides in soy beans and rices was performed by gas chromatography with dual electron-capture detection and nitrogen-phosphorus detection. The pesticides were extracted from the samples with solvent and the Bio-Beads S-X3 clean-up procedure was used. Recovery studies were performed at the 1-ppm level of pesticides added to each crop. Their recoveries ranged between 83 and 105% with coefficient of variations of 0.5-8.2%. The gas chromatographic properties of the 25 pesticides were also investigated. Conformation analysis was achieved by the retention time and characteristic fragment ions using the technique of gas chromatography-mass spectrometry-selected-ion monitoring.

Chromatography, Gas↗
PubMed1993

Phosphorylation of Ser-42 and Ser-59 in the N-terminal region of the tyrosine kinase p56lck.

Ser-42 and Ser-59 in the N-terminal region have been identified as the major phorbol ester-induced phosphorylation sites of p56lck. Phosphorylation of Ser-59 results in a gel shift from 56 kDa to 61 kDa. Simultaneous phosphorylation of Ser-42 and Ser-59 results in a further gel shift to 63 kDa. In vitro kinase assays show that Ser-59 can be uniquely phosphorylated by mitogen-activated protein kinase and that Ser-42 can be phosphorylated by either protein kinase A or protein kinase C.

Amino Acid Sequence↗
PubMed1993

A comparison of outcomes in men 11 years after heart-valve replacement with a mechanical valve or bioprosthesis. Veterans Affairs Cooperative Study on Valvular Heart Disease.

BACKGROUND: Mechanical heart valves are durable but thrombogenic, and their use requires that the patient receive anticoagulants. In contrast, bioprosthetic valves are less thrombogenic, but they have limited durability because of tissue deterioration. METHODS: To compare the outcomes of patients who receive these two types of valves, we randomly assigned 575 men scheduled to undergo aortic-valve or mitral-valve replacement to receive either a mechanical or a bioprosthetic valve. The primary end points were death from any cause and any valve-related complication. RESULTS: During an average follow-up of 11 years, there was no difference between the two groups in the probability of death from any cause (11-year probability for mechanical valves, 0.57; for bioprostheses, 0.62; P = 0.57) or in the probability of any valve-related complication (0.65 and 0.69, respectively; P = 0.39). There was a much higher rate of structural valve failure among patients who received bioprosthetic valves (11-year probability, 0.15 for the aortic valves and 0.36 for the mitral valves) than among those who received mechanical valves (no valve failures; P < 0.001). However, this difference was offset by a higher rate of bleeding complications among patients with mechanical valves than among those with bioprosthetic valves (11-year probability, 0.42 and 0.26, respectively; P < 0.001) and by a greater frequency of peri-prosthetic valvular regurgitation among patients with mechanical mitral valves than among those with mitral bioprostheses (11-year probability, 0.17 and 0.09, respectively; P = 0.05). CONCLUSIONS: After 11 years, the rates of survival and freedom from all valve-related complications were similar for patients who received mechanical heart valves and those who received bioprosthetic heart valves. However, structural failure was observed only with the bioprosthetic valves, whereas bleeding complications were more frequent among patients who received mechanical valves.

Aortic Valve↗
PubMed1993

Effect of radiation therapy and Photofrin on tissue response in a rat model.

Treatment of advanced carcinomas of the head and neck may benefit from adjuvant photodynamic therapy and brachyradiotherapy. To date, however, there has been no controlled study to evaluate whether high-dose irradiation can be safely accomplished without major tissue reaction in the presence of high circulating doses of Photofrin, the photosensitizing agent used in photodynamic therapy. Thirty adult male white rats were involved in the study. Fifteen rats received Photofrin 5 mg/kg intravenously, and 15 rats received the same volume of sterile saline intravenously. At 48 hours following injection, each rat received 1,000 cGy of radiation to a 3 x 5 cm area of dorsal skin using a cobalt linear accelerator unit. Skin changes postradiation were observed for degree of erythema, blistering, necrosis, and sloughing. Five rats from the Photofrin and control radiation groups were sacrificed on days 2, 7, and 21 postradiotherapy. Skin changes in each animal were identical with mild erythema lasting from 10-14 days postradiotherapy. There was no evidence of blistering, necrosis, or sloughing of skin in any of the animals studied. Histologic evaluation of the irradiated skin after sacrifice demonstrated no difference between the Photofrin and saline-irradiated groups. As well, the histologic recovery from acute radiation injury was also identical. This controlled study demonstrates that radiation therapy may be safely administered without increased morbidity when tissue concentrations necessary to perform photodynamic therapy are present.

Animals↗
PubMed1993

Gene transfer in bovine blastocysts using replication-defective retroviral vectors packaged with Gibbon ape leukemia virus envelopes.

With this work we demonstrate that murine leukemia virus (MLV)-based replication-defective retroviral vectors encapsidated with Gibbon ape leukemia virus (GaLV) envelopes are significantly more infectious to bovine embryonic trachea (EBTr) cells than vectors encapsidated with murine xenotropic envelope proteins. In a test of internal promoter activity in an MLV retroviral vector, the rat beta-actin promoter was shown to be better than the herpes simplex virus type 1 thymidine kinase (TK) and human cytomegalovirus (CMV) immediate early promoters for the expression of an E. coli beta-galactosidase marker gene in bovine target cells. By co-culture of bovine blastocysts and virus-producing cells, or by culture of embryos in the medium harvested from virus-producing cells, we transferred the E. coli beta-galactosidase gene into trophoblasts and also into inner cell mass (ICM) cells of a bovine embryo through the infection of the MLV-based replication-defective retroviruses encapsidated with GaLV envelope proteins. The infection was confirmed by the expression of the E. coli beta-galactosidase gene under a beta-actin internal promoter. In addition, co-culture of ICM cells with virus-producing cells resulted in differentiation of ICM cells into embryoid bodies expressing the marker genes.

Actins↗
PubMed1993

Pharmacokinetics of DepoFoam gentamicin delivery system and effect on soft tissue infection.

Infections of burn and soft tissue wounds are often difficult to treat with systemic antibiotics since drug delivery to the wound may be suboptimal and high doses may result in toxicity. DepoFoam particles, a novel lipid-based drug delivery system, are composed of phospholipid membranes, enclosing multiple aqueous chambers into which pharmacologic agents can be encapsulated for local drug delivery. We encapsulated gentamicin (GENT) in DepoFoam particles with an average yield of 81% +/- 8 SD for 10 preparations. Encapsulated GENT was incubated in human plasma with t1/2 of 21 days, demonstrating stability in vitro. In vivo pharmacokinetics were determined by injecting CF-1 mice subcutaneously (sc) with a single dose of 0.5 mg of free (nonencapsulated drug) or DepoFoam GENT. At intervals postinjection the sc tissue was excised and blood was obtained by inferior cava puncture and both were assayed for GENT levels. At 0.5, 2, 6, and 24 hr following drug administration there was a significant difference between GENT levels in the tissue achieved with the encapsulated drug and free drug with n = 3-4 at each time point for each group (P < 0.01). By 24 hr following administration of free drug there was minimal detectable GENT in the tissues, while therapeutic levels of GENT remained in tissue at 24 hr following DepoFoam GENT injection. Serum GENT peaked at 30 min for both the DepoFoam (5 micrograms/ml) and free drug (10 micrograms/ml) and was undetectable by 2 hr (n = 3 each group).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

A slow-release methotrexate formulation for intrathecal chemotherapy.

Optimal anticancer treatment with cell cycle phase-specific antimetabolites requires a sustained maintenance of cytotoxic drug levels. However, drugs that can be administered intrathecally have short half-lives in cerebrospinal fluid (CSF) and require repeated administrations by lumbar punctures, which are painful and inconvenient. Implantable pumps are expensive and require surgery. In a rat model, a lipid-based formulation of methotrexate (Depo/methotrexate) was tested for extended maintenance of therapeutic CSF concentration after a single injection. The half-life of methotrexate in CSF after an intracisternal injection of Depo/methotrexate was 5.4 days compared to 0.30 days for unencapsulated methotrexate. This 18-fold increase in methotrexate half-life may make Depo/methotrexate useful for intrathecal chemotherapy of neoplastic meningitis.

Animals↗
PubMed1993

Extended-release formulation of morphine for subcutaneous administration.

Pain arising from cancer tends to be chronic and chemotherapy of cancer pain usually requires narcotics. Most injectable narcotics, however, have short half-lives (T1/2) and require either continuous infusion or repeated frequent injections which are both inconvenient and uncomfortable. An extended-release formulation of morphine sulfate (Depo/Morphine) in a lipid-based drug-delivery system was characterized and tested in an animal model. The encapsulation efficiency was 53% +/- 4%, and the in vitro release T1/2 in human plasma at 37 degrees C was 12.1 +/- 1.1 days. Following s.c. administration of Depo/Morphine, the total amount of morphine remaining at the s.c. injection site decreased monoexponentially with a T1/2 value of 2.59 +/- 0.16 days as compared with 0.46 +/- 0.04 h following the injection of unencapsulated morphine. The morphine concentration in plasma also decreased monoexponentially with a T1/2 value of 8.33 +/- 2.13 days as compared with 0.45 +/- 0.21 h for unencapsulated morphine. Cataleptic behavior was observed in mice injected with unencapsulated morphine but not in those given an identical dose of morphine in the form of Depo/Morphine. In conclusion, Depo/Morphine has potential as an extended-release formulation of morphine and may be useful in chemotherapy of cancer pain as well as in maintenance therapy of narcotic addicts.

Animals↗
PubMed1993

Relationship between aromatase activity and steroid receptor levels in ovarian tumors from postmenopausal women.

Aromatase activity, as well as steroid receptors, exists in nonfunctional ovarian tumors. Steroid receptor status has been reported to be related to prognosis in ovarian cancer patients. We determined aromatase activity and progesterone receptor (PR) and estrogen receptor (ER) levels in 43 ovarian tumors obtained from postmenopausal women. Aromatase activity was detected in 35 tumors (81%), PR in 21 tumors (49%) and ER in 13 tumors (30%). Eighty-three percent (10/12) of mucinous cystadenoma tissues showed positive PR with high aromatase activity, while 93% (13/14) of malignant tumors showed negative PR and low aromatase activity. Aromatase activity was detected in 95% (20/21) of PR-positive tumors, being greater than in PR-negative tumors (P < 0.002). There was a positive correlation between aromatase activity and PR (rs = 0.49, P < 0.001). However, there was no correlation between aromatase activity and ER. In 17 patients (43%), the serum estradiol level was higher than 30 pg/ml and there was a positive correlation among estradiol, estrone, androstenedione and testosterone. However, serum steroid levels were not correlated with aromatase activity, PR or ER. Aminoglutethimide inhibited aromatase activity of benign and malignant ovarian tumors, uterine myoma, choriocarcinoma cells and purified human placental P-450arom in a similar manner. These results suggest that aromatase activity is correlated with PR in ovarian tumors of postmenopausal women. In addition to steroid receptor status, aromatase activity may be a useful prognostic factor in ovarian cancers.

Adult↗
PubMed1993

Growth suppression of MCF-7 human breast cancer cells by aromatase inhibitors: a new system for aromatase inhibitor screening.

In our previous study we found that MCF-7 cells possess aromatase activity and stimulate estrogen receptor-mediated growth. The pathways through which androgens are converted to estrogens by aromatase and estrogens interact with estrogen receptors contribute significantly to growth stimulation. The administration of aromatase inhibitor results in suppression of growth stimulation by androgens. This system enabled us to assess directly the biological activities of aromatase inhibitors. Aromatase activity was inhibited in a dose-dependent manner by the addition of aminoglutethimide and CGS 16949A, competitive inhibitors, and of 14 alpha-hydroxy-4-androstene-3,6,17-trione and 4-hydroxy-androstenedione, mechanism-based inhibitors. After preincubation with mechanism-based inhibitors, aromatase activity was significantly suppressed, whereas after preincubation with competitive inhibitors, it was adversely increased. These effects were concentration- and time-dependent. Preincubation with competitive inhibitors resulted in augmentation of subsequent androgen stimulation of thymidine incorporation, while preincubation with mechanism-based inhibitors resulted in diminished stimulation by subsequent androgen administration. These results suggest that in MCF-7 cells competitive inhibitors adversely induce aromatase and accelerate the subsequent androgen stimulation of DNA synthesis. Suicide inhibitors are more effective than competitive inhibitors. This system will be useful for aromatase inhibitor screening.

Aminoglutethimide↗
PubMed1993

[Relationship among aromatase activity, estrogen receptor and progesterone receptor in ovarian tumors from postmenopausal women].

Aromatase activity, as well as steroid receptors, has been demonstrated in ovarian tumors. Aromatase activity was detected in 35 tumors (81%), PR in 21 tumors (49%) and ER in 13 tumors (30%) out of 43 ovarian tumors (27 benign, 14 malignant and 2 granulosa cell tumors). Moreover, immunohistochemical study demonstrated aromatase cytochrome P-450 (P-450arom) in the tumor tissues. Aromatase activity was significantly greater in PR-positive tumors than in PR-negative tumors (p < 0.002). There was a positive correlation between aromatase activity and the PR level (rs = 0.490, p < 0.001). Thirteen of 14 (93%) malignant tumors showed negative PR with low aromatase activity. However, the presence of ER was not correlated with aromatase activity or the presence of PR. There was a positive correlation among serum levels of estradiol, estrone, androstenedione and testosterone, whereas the serum steroid levels were not correlated with aromatase activity, the PR or ER of ovarian tumors. These results suggest that aromatase activity is correlated with PR in ovarian tumors of postmenopausal women.

Adult↗
PubMed1993

[Two cases of improved quality of life with intra-arterial infusion of CDDP or unresectable gallbladder and pancreatic cancer].

The prognosis of patients with advanced gallbladder and pancreatic cancers is poor. Intra-arterial infusion chemotherapy with CDDP was imported in patients with unresectable gallbladder cancer (First case) and pancreatic cancer (Second case). The values of CEA and CA 19-9 were reduced after chemotherapy in the first case, but the CA 19-9 level was not reduced in the second case. Their hospital free survival (HFS) has been more than one year and they could return to their respective occupations. QOL was thought to be improved when considering their HFS. Intra-arterial infusion of CDDP might be one of the multimodal therapies to improve QOL for patients with unresectable gallbladder and pancreatic cancers.

Cisplatin↗
PubMed1993

Outcome of BMT during first complete remission of AML: a comparison of two sequential studies by the Children's Cancer Group.

One hundred and fifty children with AML in first remission were treated with allogeneic BMT in two sequential studies of the Childrens Cancer Group. The absence of differences in baseline variables justified comparison between the two studies. In the initial study (CCG-251), patients received GVDH prophylaxis with MTX alone (17 doses over 102 days). In an attempt to diminish the morbidity and mortality of acute GVDH, a second study (CCG-213) employed stronger GVHD prophylaxis with 6 months of CYA and short-course MTX (four doses over 11 days). Outcome was compared between these two non-randomized populations of children with AML transplanted in first remission. Augmented GVHD prophylaxis substantially diminished treatment-related mortality from 31% to 11% (p = 0.0033), but this effect was counterbalanced by an increase in the relapse risk from 22% to 35% (p = 0.29). Event-free survival at 2 years was 54% on CCG-251 and 59% on CCG-213 (p = 0.21). We observed a marginal diminution of relapse risk among patients with chronic GVHD compared with those without chronic GVHD (19% vs. 35%, respectively; p = 0.10). No anti-leukemic effect of acute GVHD was observed.

Adult↗
PubMed1992

Impact of a galanin antagonist on exogenous galanin and natural patterns of fat ingestion.

The peptide galanin (GAL) has a potent stimulatory effect on fat ingestion after administration into the hypothalamic paraventricular nucleus (PVN). This study examined a newly synthesized GAL antagonist, M40, in two separate experiments involving: (1) PVN injections of M40 alone in freely feeding animals, to investigate the importance of endogenous GAL receptor activity in determining natural patterns of fat ingestion, and (2) PVN injections of M40 in combination with exogenous GAL, to determine whether endogenous GAL receptors mediate this peptide-induced response. The results demonstrate that PVN injection of M40 by itself dose-dependently (2-108 pmol) reduces spontaneous ingestion of the fat diet. This phenomenon is robust, behaviorally specific and opposite to that induced by GAL itself. Moreover, the stimulatory effect of PVN-injected GAL on fat ingestion can be blocked by prior PVN administration of M40 at relatively low doses (2-6 pmol), indicating that M40 is a potent antagonist of GAL receptors in the hypothalamus. Together, these results provide the first evidence for the existence of endogenous GAL receptors in mediating the action of exogenous GAL in the hypothalamus. They also constitute a crucial step in demonstrating a physiological function of these PVN GAL receptors in controlling natural patterns of fat ingestion.

Animals↗
PubMed1992

[CT assessment of gallbladder opacification 12-24 hours after angiography].

After the injection of conventional contrast agents that are largely excreted in urine, gallbladder opacification is observed in patients with renal dysfunction. However, some reports have noted that gallbladder opacification on plain radiographs occurs frequently in patients without renal impairment after the intravenous administration of Ioxaglate, one of the new low-osmolality agents. We carried out CT examination 12-24 hours after angiography with various kinds of contrast media in 437 patients to examine the incidence of gallbladder opacification. The influence of hepatobiliary and renal function on the excretion of contrast medium is discussed. Gallbladder opacification was observed in more than 60% of the patients. This result indicates that gallbladder opacification is not a rare phenomenon, and is even common in delayed CT examinations of patients with normal renal function. The high frequency of gallbladder opacification was recognized not only in the renal dysfunction group but also in the normal liver function group. Gallbladder opacification in delayed CT examination shows that the hepatobiliary tract is important in the excretion of contrast medium.

Adolescent↗
PubMed1992

Unrelated donor bone marrow transplantation for correction of lethal congenital immunodeficiencies.

Unrelated donor marrow transplantation was undertaken in eight infants with severe combined immunodeficiency (SCID) and two children each with Wiskott-Aldrich syndrome (WAS) and Chediak-Higashi syndrome (CHS) who did not have histocompatible siblings. Donors for three patients were phenotypically matched at all HLA-A, B, Dr, and Dw loci, whereas nine donors were mismatched from the recipients at one of the HLA-A or B loci but phenotypically identical at evaluable D loci. All but one patient received conditioning chemotherapy and/or radiotherapy before infusion of donor marrow, which was not T-cell depleted. Prophylaxis for graft-versus-host disease (GVHD) consisted of methotrexate and prednisone combined with either cyclosporine A (six patients), antithymocyte globulin (five patients), or anti-CD5 ricin A chain immunotoxin (one patient). All patients engrafted with donor cells, and only 4 of 12 experienced any GVHD (1 of 8 SCID, 1 of 2 WAS, 2 of 2 CHS). Two children who developed grade II and two who developed grade III GVHD were successfully treated and all are now alive, off immuno-suppressive therapy, with no evidence of chronic GVHD greater than 18 months after transplant. Ten patients are alive with excellent immunoreconstitution greater than or equal to 1 year to greater than or equal to 3 years after transplant; actuarial survival is predicted to be 83% with a median follow-up of 2 years. Two children with SCID succumbed to pre-existing opportunistic infection early posttransplant. We conclude that closely matched unrelated donor bone marrow transplantation can correct congenital immunodeficiencies including variants of SCID, WAS, and CHS, with an acceptably low incidence of transplant-related complications, principally GVHD.

Bone Marrow Transplantation↗