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Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 541 records · Page 30Linked to original sources

Variation in the response of T cells to concanavalin A after in vitro exposure to benzo[A]pyrene and 2-aminofluorene.

The ability of the polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BP) and its metabolites to be immunosuppressive has been well documented by many investigators. The arylamine, 2-aminofluorene (AF) and its metabolic intermediates have not been as widely studied in this regard. Here, we investigate the effect of BP, 3-hydroxy-BP (3-OH-BP), AF, N-hydroxy-AF (N-OH-AF) and acetyl-AF (AAF) on T-cell proliferation using the T-cell mitogen, Concanavalin A (ConA). These compounds as well as BP-7, 8-diol-9, 10-epoxide (BPDE) were also used to determine their effect on T-cell-mitogen binding. Both AF and BP are substrates for the P-450 and flavin-containing monooxygenase enzyme system, which can be induced with beta-naphthoflavone (beta NF). We incubated beta nF with BP and AF to determine the effect of a P-450 inducer on BP and AF mediated-ConA suppression. Here we demonstrate that BP, 3-OH-BP, AF, and AAF are able to suppress the proliferative response to ConA, while N-OH-AF cannot. Further, we show that BP, 3-OH-BP, BPDE, AF and N-OH-AF do not alter the ability of ConA to bind the mitogen receptor of splenic T-cells, indicating an intracellular mechanism for suppression. Studies with beta NF indicate that this P-450 inducer enhances the anti-proliferative effect of BP, while it abolishes this effect of AF.

Animals↗

High-dose cytarabine and recombinant human granulocyte colony-stimulating factor for the treatment of resistant acute myelogenous leukemia.

Few salvage treatments are successful for patients with relapsed acute myelogenous leukemia after a short first remission, multiple relapses, or for patients with disease refractory to initial induction chemotherapy. To improve the results of salvage therapy we studied the efficacy and toxicity of a combination of G-CSF (5 mu tg/kg IV q day) used as a priming agent followed by continued exposure to G-CSF and high-dose cyatarabine (2 gm/m(2) IV q 12 hours x 12 doses) in fifteen adult patients with relapsed or refractory acute myelogenous leukemia. Nine of fourteen (64%; 95% confidence interval 35 to 87%) achieved complete remission, four failed to enter remission and one died of multiorgan system failure after progressive leukemia cutis despite chemotherapy-induced bone marrow aplasia. Median disease-free survival is 148 days and median survival from study entry for responding patient is 174 days. Three patients who achieved complete remission subsequently relapsed with a median time to relapse of 147 days. Median time to granulocyte >0.5 x 10(9)/L was 22 days (19 to 34 days) and the median time to platelet recovery >20 x 10(9)/L was 30 days (23 to 214 days). Although gastrointestinal toxicity was common, no patient developed severe cardiac, hepatic, pulmonary, or neurologic complications. An elevation in the percent of bone marrow blasts in S-phase after 48 hours of treatment with G-CSF was identified in 7 of 12 evaluable patients. These results demonstrate that the combination of G-CSF and high-dose cytarabine may be used as an effective salvage treatment for patients with resistant acute myelogenous leukemia.

Acute Disease↗

Disseminated ependymomas of the central nervous system.

Ependymomas are rare central nervous system (CNS) neoplasms that occasionally disseminate along the neuraxis or to extraneural sites. Definitive criteria predictive of dissemination have yet to be determined. One hundred forty patients with CNS ependymoma (88 primary spinal and 52 primary intracranial tumors) were surgically treated by the senior author (F.J.E.) between 1986 and 1994. Sixteen patients (11.4%) demonstrated tumor dissemination. The disseminated group consisted of 11 (12.5%) of 88 primary spinal and five (9.6%) of 52 primary intracranial ependymomas. The authors retrospectively reviewed the patients with CNS ependymoma and have identified several characteristics associated with dissemination from the primary tumor site. The mean time from diagnosis to dissemination was 6.8 years. The patients with disseminated disease were younger (16.8 vs. 28.3 years old, p = 0.02), had fewer gross-total resections (29% vs. 68%, p = 0.015), and had tumors with higher proliferative indices (MIB-1 staining, 13.14% vs. 2.06%, p = 0.02). High-grade tumors had a mean proliferation index of 21%, versus 2.4% and 1.6% for myxopapillary and low-grade tumors, respectively (p = 0.0003). In contrast to previous studies, tumor histology was the most significant variable for time to dissemination as determined by multivariate analysis (p = 0.008). Myxopapillary and high-grade tumors were 3.6 and 5.6 times more likely to have a shorter time to dissemination than low-grade tumors. In addition, dissemination is associated with a worse prognosis. At follow-up review, 31% of patients with disseminated disease had died compared to 7% of patients without dissemination (p = 0.04). It is concluded that younger patients with subtotal resections, myxopapillary or high-grade histology, and tumors with high proliferative indices are at substantial risk for the development of disseminated disease during their clinical course.

Adolescent↗

Differentiation of Korean isolates of Entamoeba histolytica from Entamoeba dispar.

Cysts of Entamoeba histolytica are still found from humans in Korea, but not all of the cysts are known as pathogenic. The non-pathogenic strain is regarded as a different species, E. dispar. In this study, Korean isolates of conventional E. histolytica were subjected for the differentiation by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Human stools were screened by routine microscopic examination, and cyst or trophozoite positive stools were inoculated into Robinson media. The cultivated trophozoite positive stools were inoculated into Robinson media. The cultivated trophozoites were prepared for DNA extraction, and the DNAs were used for PCR with common primers of P1 gene. The PCR products were digested with 3 restriction enzymes and RFLP was observed. Also anti-sense primers containing the cleavage site of each restriction enzyme were designed for differentiation only by PCR. The PCR products of Korean isolates S9, S12, YS-6, and YS-27 were spliced by Taq I and Xmn I but not by Acc I, and the isolates S1, S3, S11, S15, S16, S17, S20, YS-17, and YS-44 were spliced by Acc I but not by Taq I and Xmn I. These RFLP pattern correlated well with PCR products by the species specific primers. The findings confirm that the Korean isolates S9, S12, YS-6, and YS-27 are E. histolytica and others are E. dispar. In Korea, most of the asymptomatic cyst carriers are infected by E. dispar, not by E. histolytica.

Animals↗

Differentiation of Entamoeba histolytica and Entamoeba dispar in cyst-passers by immunoblot.

Differentiation of invasive strains of Entamoeba histolytica according to their pathogenicity has been a topic of long debate, but now the pathogenic species only is regarded as E. histolytica while the non pathogenic species is E. dispar. The present study applied immunoblot to differentiate infections of the two species among microscopically-detected cyst-passers in Korea. The crude extract of E. histolytica separated in 5.20% gradient gels, revealed many fractions of 94, 81, 71, 50, 44, 38.5, 37.5, 29, 19, and 18 kDa when the cysteine proteinase inhibitor, E64, was supplemented. The scrum IgG antibody of 3 proven E, histolytica cases reacted with the antigenic fractions of 117, 110, 99, 68, 66, 60, 54, 52, 46, and 45 kDa. Sera of PCR confirmed 3 cases of E. dispar reacted only to the 117 kDa fraction of the E. histolytica crude extract which was regarded as non-specific. To the antigen of monoxenic E. dispar, sera of E. dispar and E. histolytica cases showed the same immunoblot reactions. The serum IgA antibody reacted with several antigenic fractions of both E. histolytica and E. dispar, but IgM and IgE antibodies showed no reaction to either antigen. Sera of 24 symptomless amebic cyst passers were screened with the E. histolytica antigen; two were found to be infected by E. histolytica and 22 were by E. dispar. The present findings suggest that in Korea most of asymptomatic cyst passers of E. histolytica are carriers of E. dispar. Immunoblot using E. histolytica antigen is a good technique for the differentiation of E. histolytica and E. dispar infections.

Animals↗

Improvement of thrombocytopenia due to hypersplenism after transjugular intrahepatic portosystemic shunt placement in cirrhotic patients.

Thrombocytopenia secondary to hypersplenism is a well-known complication of portal hypertension. The effects of transjugular intrahepatic portosystemic shunt (TIPS) on hypersplenism have not been adequately studied. In this report, we describe 11 patients who had significant improvement in their thrombocytopenia due to hypersplenism after TIPS. There was a statistically significant improvement in the platelet counts after TIPS placement, in virtually every case during the follow-up period, although some patients had platelet counts less than 100,000/mm3 at the end of the follow-up period. Statistically significant hemodynamic improvement in the gradient pressure was observed immediately after TIPS. Furthermore, all patients tolerated the procedure well, and TIPS-related complications were encountered during the follow-up period. Our data suggest that TIPS is an effective, noninvasive alternative to surgical interventions in the management of hypersplenism in cirrhotic patients, who are generally high-risk surgical candidates.

Adult↗

[Isolated rupture of the ventricular septum caused by nonpenetrating trauma--a case report of operation in acute stage].

We experienced a case of the isolated ventricular septal defect due to nonpenetrating chest trauma. The patient was 22-year-old male who hit his chest with a steering wheel on car accident. The echocardiogram examined on the next day revealed a ventricular septal defect. Four days after the injury, intracardiac repair was performed. On cardiopulmonary bypass the ventricular perforation (35 x 35 mm size) located in the muscular portion near the apex was closed with a PTFE and equestrian pericardial patch. Postoperative cardiopulmonary function could improve enough to wean from IABP and respiratory support. However, the patient died on the fifth postoperative day of severe hepatic failure due to profound shock persisted after the accident.

Accidents, Traffic↗

Work-site variation in managerial drinking.

To assess cross-work-site variation in the general drinking behaviors (on and off the job) of employees, we conducted a cross-sectional survey of managers (n = 7255) at 114 places of work located throughout the continental United States. The work-site mean for the total number of drinks consumed on a typical drinking day ranged from 1.4 to 3.17, a two-fold differential. Regression analysis showed an independent work-site effect, controlling for respondents demographics and type of work. This finding suggests that modifiable work-site characteristics could influence what employees drink on and off the job.

Administrative Personnel↗

Sodium hyaluronate eyedrops enhance tear film stability.

Sodium hyaluronate eyedrops can relieve various dry eye symptoms by prolonging the stability of the precorneal tear film. To determine the most effective concentration of sodium hyaluronate, we studied the concentration-dependent effects of sodium hyaluronate eyedrops on the precorneal tear film breakup time (BUT) in 12 volunteers. These subjects had a BUT of 10 seconds or less and a low tear volume determined with the phenol red thread test. They received four different concentrations of sodium hyaluronate eyedrops (0, 0.05, 0.1 and 0.3%). BUT was measured noninvasively using a non-contact specular microscope before the sodium hyaluronate eyedrop instillation and again after 5, 15, 30, 60, 120 and 180 minutes. The tear film stability period was prolonged significantly with 0.1% and 0.3% eyedrops at all measurement times (P < 0.05), while the eyes treated with 0% and 0.05% eyedrops showed no significant prolongation of tear film stability at any measurement times. The findings of this study confirm that sodium hyaluronate at a concentration of at least 0.1% is required to delay the breakup of the precorneal tear film.

Adult↗

Age-related changes in gastric blood flow in rats.

The present study was designed to examine the influence of aging on the gastric blood flow, a major mucosal protective mechanism against experimental gastric mucosal injury, basally and after treatment with acid, a known stimulant of gastric blood flow. Our data demonstrated that aging was associated with a significant decline in basal gastric blood flow (both mucosal and serosal). However, there were no significant differences in acid-induced increases in gastric blood flow between the young and aged animals. These findings suggest that aging is associated with selective and specific reductions in mucosal protective mechanisms that may predispose aged animals to gastric mucosal injury.

Aging↗

Cell-permeable ceramide inhibits the growth of B lymphoma Raji cells lacking TNF-alpha-receptors by inducing G0/G1 arrest but not apoptosis: a new model for dissecting cell-cycle arrest and apoptosis.

We examined the effects of a cell-permeable ceramide analog, C2-ceramide, on the growth of TNF-alpha-resistant B lymphoma Raji cells lacking TNF-alpha-receptors (TNF-R). C2-ceramide inhibited the clonal growth of not only TNF-alpha-sensitive myeloid leukemia cells (HL60 and U937) but also Raji cells. Following stimulation with C2-ceramide, HL60 and U937 cells showed apoptotic cell death, whereas Raji cells did not show a detectable level of apoptosis. However, a cell-cycle arrest in G0/G1 phase was observed in Raji cells after the treatment with C2-ceramide, which was accompanied by the dephosphorylation of retinoblastoma (RB) gene products and decreased expression of p53 proteins. Failure of C2-ceramide to induce apoptosis in Raji cells might be explained by the lack or low expression of apoptosis-inducing proteins by two lines of evidence: (1) Raji cells were resistant to apoptosis induced by ceramide even in the presence of transcription/translation inhibitors; (2) Bax protein expression was not detectable in Raji cells, although Bcl-2 protein expression in Raji cells was even less than that in HL60 and U937 cells. Moreover, protein kinase C (PKC), whose activation has been described to inhibit ceramide-induced apoptosis, inhibitor H-7 did not induce apoptotic cell death in Raji cells, suggesting that an imbalance between PKC and ceramide pathways is not the reason for the resistance of Raji cells against ceramide-induced apoptosis. Finally, ceramide-induced activation of nuclear factor kappaB (NF-kappaB) was observed in Raji cells as well as HL60 cells, indicating that activation of this molecule may not be specific for apoptosis. By using the present model, one can dissect cell-cycle arrest and apoptosis induced by ceramide.

Apoptosis↗

[Levels of atrial natriuretic peptide in stable and exacerbated chronic obstructive pulmonary disease].

Plasma Atrial Natriuretic Peptide (ANP) levels are elevated in patients wish chronic obstructive pulmonary disease (COPD) and can play a role in oedema formation. Plasma ANP levels measured in 60 patients with COPD were compared with results of pulmonary haemodynamics, with therapeutic response to treatment in the time of exacerbation of COPD and with physiologic status of patients with stable COPD. Plasma ANP levels did not correlate with right atrial and pulmonary artery pressure, but were significantly related with right ventricular end diastolic volume and with right ventricular wall volume measured by magnetic resonance imaging. Oxygen breathing (2 l/min by nasal prongs in 30 min.) did not change either mean pulmonary artery pressure or ANP levels. Among patients studied during an acute exacerbation of COPD, plasma ANP levels were higher in patients with oedema (302 +/- 185 pg/ml) than in patients without oedema (87 +/- 43 pg/ml). Oxygen therapy applied in one hour did not influence plasma ANP levels. Plasma ANP levels decreased during first three days of treatment in patients with oedema. This decrease was related to the body weight. In the group of patients with hypoxemia in stable COPD, plasma ANP levels (120 +/- 50 pg/ml) were higher in patients with the history of hypercapnia and oedema than in others (54 +/- 15 pg/ml).

Aged↗

Comparative genetic and QTL mapping in sorghum and maize.

DNA markers and genetic maps will be important tools for direct investigations of several facets of crop improvement and will provide vital links between plant breeding and basic plant biology. The markers and maps will become more important for increased crop production because plant genetics will be required to extend or replace extant management practices such as chemical fertilizers, pesticides, and irrigation (Lee, 1995). Despite the importance of the sorghum crop, comprehensive genetic characterization has been limited. Therefore, the primary goal of this research program was to develop basic genetic tools to facilitate research in the genetics and breeding of sorghum. The first phase of this project consisted of constructing a genetic map based on restriction fragment length polymorphisms (RFLPs). The ISU sorghum map was created through linkage analysis of 78 F2 plants of an intraspecific cross between inbred CK60 and accession P1229828 (Pereira et al., 1994). The map consists of 201 loci distributed among 10 linkage groups covering 1,299 cM. Comparison of sorghum and maize RFLP maps on the basis of common sets of DNA probes revealed a high degree of conservation as reflected by homology, copy number, and collinearity. Examples of conserved and rearranged locus orders were observed. The same sorghum population was used to map genetic factors (mutants and QTL) for several traits including vegetative and reproductive morphology, maturity, insect, and disease resistance. This presentation will emphasize analysis of genetic factors affecting plant height, an important character for sorghum adaptation in temperate latitudes for grain production. Four QTL for plant height were identified in a sample of 152 F2 plants (Pereira and Lee, 1995) whereas 6 QTL were detected among their F3 progeny. These observations and assessments of other traits at 4 QTL common to F2 plants and their F3 progeny indicate some of these regions correspond to loci (dw) previously identified on the basis of alleles with highly qualitative effects. Four of the six sorghum plant height QTL seem to be orthologous to plant height QTL in maize. Other possible instances of orthologous QTL included regions for maturity and tillering. These observations suggest that the conservation of the maize and sorghum genomes encompasses sequence homology, collinearity, and function. The genetic information and technology developed on the basis of DNA markers could be used in several facets of breeding, genetics, and other basic biological investigations. In addition, DNA markers have been used to survey large collections of elite sorghum germ plasm to determine the degree of genetic relationships and genetic diversity (Ahnert et al., 1996). RFLP data seem to portray genetic relationships more accurately than the methods based exclusively on the coancestry coefficient. This information provides the basis for more accurate perceptions of genetic relationships and diversity.

Adaptation, Physiological↗

CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation.

Donor lymphocyte infusions can reinduce complete remission in the majority of patients with chronic myelogenous leukemia (CML) who relapse into chronic phase after allogeneic bone marrow transplantation (BMT). Such infusions are associated with a high incidence of graft-versus-host disease (GVHD) and marrow aplasia. BMT using selective depletion of CD8+ lymphocytes from donor cells reduces the incidence of GVHD without an increase in leukemia relapse. We hypothesized that infusion of CD8-depleted donor peripheral blood lymphocytes could also reinduce complete remissions with a lesser potential to produce symptomatic GVHD in patients with CML who relapsed after allogeneic BMT. Ten patients with Ph(+) CML who relapsed a median of 353 days after BMT (range, 82 to 1,096 days) received donor lymphocyte infusions depleted of CD8+ cells. Nine patients received a single infusion and 1 received two infusions. Four patients were treated while in chronic phase with clonal evolution, 2 during accelerated phase, 3 during blast crisis, and 1 in a cytogenetic relapse. A mean of 0.9 +/- 0.3 x 10(8) mononuclear cells/kg were infused, containing 0.6 +/- 0.4 x 10(6) CD3+CD8+ cells/kg. Six patients achieved hematologic and cytogenetic remission at 4, 8, 11, 15, 39, and 54 weeks after lymphocyte infusion. Two patients developed > or = grade II acute GVHD, and 1 patient developed mild chronic GVHD. We conclude that donor lymphocyte infusions depleted of CD8+ cells can induce remissions with a low rate of severe acute GVHD in patients with CML who relapse after allogeneic BMT, supporting the hypothesis that CD8+ lymphocytes are important effectors of GVHD, but may not be essential for the graft-versus-leukemia effect against this disease. Further controlled studies are required to confirm these preliminary observations.

Acute Disease↗