Biomedical subjects

B K Lee

Publications and source records attributed to B K Lee.

At least 73 records · Page 4Linked to original sources

PubMed1996

Assessing myocardial perfusion with Albunex during coronary artery bypass surgery: technical considerations and safety of aortic root injections.

OBJECTIVE: To test the safety and report on limiting technical considerations, including optimal dosing of Albunex (Molecular Biosystems, Inc, Mallinckrodt Medical, St. Louis, MO) for myocardial opacification after intra-aortic root injections during cardiac surgery. DESIGN: This was a prospective randomized study with a control group who did not receive Albunex and a group who received intra-aortic root injections of Albunex. SETTING: Multicenter (two) independent university hospitals. PARTICIPANTS: 32 patients scheduled for elective coronary artery bypass surgery were evaluated after individual informed consent was obtained. INTERVENTIONS: 2 to 8 mL of Albunex were injected before and after coronary revascularization. MEASUREMENTS AND MAIN RESULTS: Quality of enhancement in each of four regions of the left ventricle was assessed from a short-axis mid-papillary ultrasound image by three experienced observers blinded to dose. Electrocardiogram (ECG), creatine phosphokinase (CPK) (MB fraction), and hemodynamics were evaluated at baseline and throughout the study period for up to 72 hours. No differences were noted between groups with respect to preoperative and postoperative CPK enzymes (CPK-MB fraction), ECG changes, hemodynamics, requirements for separation from CPB, need for postoperative inotropes, time to extubation, and time to discharge from the intensive care unit. The average total dose of Albunex injected was 19 mL +/- 4 (0.25 mL/kg). A single dose of 4.2 +/- 1.2 mL (0.05 mL/kg) appeared to offer optimal enhancement of contrast effect for myocardial perfusion assessment. CONCLUSION: Albunex is safe and easy to use for myocardial opacification when administered via an antegrade cardioplegia catheter into the aortic root during CPB.

Aged↗

PubMed1996

Sex-determining genes on mouse autosomes identified by linkage analysis of C57BL/6J-YPOS sex reversal.

A powerful approach for identifying mammalian primary (gonadal) sex determination genes is the molecular genetic analyses of sex reversal conditions (that is, XX individuals with testicular tissue and XY individuals with ovarian tissue). Here we determined the number and chromosomal location of autosomal and X-linked genes that cause sex reversal in C57BL/6J (B6) mice carrying a Y chromosome of Mus domesticus poschiavinus origin (YPOS). B6 XYPOS mice develop either as females with exclusively ovarian tissue or as true hermaphrodites with ovarian and testicular tissue. In contrast, the YPOS chromosome is fully masculinizing on most other inbred strain backgrounds. B6-YPOS sex reversal appears to result from the incompatibility of the Sry (sex determining region, Y chromosome) allele carried on the YPOS chromosome with B6-derived autosomal or X-linked loci. We found strong evidence for the location of one gene, designated tda1 (testis-determining, autosomal 1), at the distal end of Chromosome (Chr) 4 and a second gene, tda2, in the central region of Chr 2. A third gene, tda3, on Chr 5 is implicated, but the evidence here is not as strong. We suggest that B6 alleles at these loci predispose XYPOS fetuses to ovarian tissue development, but no single locus or combination of loci is necessary and sufficient to cause sex reversal. The TDA proteins may regulate Sry expression or form complexes with the SRY protein to regulate other genes, or the tda genes may be activated or repressed by the SRY protein.

Animals↗

PubMed1995

Associations of delta-aminolevulinic acid dehydratase genotype with plant, exposure duration, and blood lead and zinc protoporphyrin levels in Korean lead workers.

Previous studies have suggested that polymorphisms in delta-aminolevulinic acid dehydratase (ALAD), a heme synthetic enzyme, may be associated with differences in blood lead levels, perhaps due to differential binding of lead in erythrocytes. The authors examined associations of ALAD genotype with blood lead and zinc protoporphyrin (ZPP) levels, exposure duration, sex, and plant in 308 currently exposed lead workers in three lead storage battery manufacturing plants in the Republic of Korea in 1993. The overall prevalence of the variant allele, ALAD2, was 11%, but prevalence varied by plant (p = 0.02: 8.6% in plant A, 20% in plant B, and 22% in plant C). While ALAD2 was not associated with mean blood lead levels, the allele was associated with blood lead levels greater than or equal to 40 micrograms/dl (crude odds ratio (OR) = 2.6, 95% confidence interval (CI) 1.1-6.3; adjusted OR = 2.3, 95% CI 0.8-6.2, with adjustment for sex, plant, and exposure duration) and with exposure durations greater than 6 years (adjusted OR = 2.5, 95% CI 1.2-5.4, with adjustment for blood lead, sex, and plant). Among workers in plant C, the highest exposure plant, ALAD2 was associated with lower ZPP levels when controlling for blood lead levels. These data suggest that lead toxicokinetics may be modified by ALAD genotype and that ALAD2 may be protective for the health effects of lead. ALAD genotype also appears to have been a selection factor for current lead exposure status in the studied workers.

Adult↗

PubMed1995

Dietary intake of cadmium and lead among the general population in Korea.

This survey was conducted in Seoul, Pusan, Chunan, and Haman in Korea to clarify cadmium and lead burden in the general Korean populations in terms of dietary intake of cadmium and lead and the concentrations of the two metals in blood. People who participated in the study were 141 healthy nonsmoking women aged 21-56 years. Determination of cadmium and lead in 24-hr food duplicates and blood samples was carried out by graphite furnace atomic absorption spectrophotometry. The geometric means for the four sites in combination were 21.2 micrograms/day for dietary cadmium, 20.5 micrograms/day for dietary lead, 1.27 ng/ml for blood cadmium, and 44.3 ng/ml for blood lead. Cadmium intake from boiled rice accounted for 23% of total daily cadmium intake. The counterpart value for lead intake from boiled rice was 12%. Blood cadmium levels and dietary cadmium intake were lower and blood lead level and dietary lead intake were higher in Korean women than in Japanese women. The values for dietary cadmium are similar to, and the values for dietary lead are somewhat lower than, the levels reported from Europe and the United States. Dietary intake was the main source of cadmium exposure, whereas lead exposure was from both ambient air and foods in the Korean population.

Adult↗

PubMed1995

Retrograde-delivered cardioplegia is not distributed equally to the right ventricular free wall and septum.

Right ventricular myocardial protection during cardiac surgery continues to be a challenge. Retrograde delivery of cardioplegia has been shown to perfuse left ventricular regions subtended by critical coronary stenosis and not adequately protected by antegrade delivery. However, the distribution of cardioplegia from the coronary sinus to the right ventricle remains in question. A reliable means for assessing such flow distribution intraoperatively is provided by contrast echocardiography. It was hypothesized that conventional use of coronary sinus catheters for retrograde cardioplegia delivery does not reliably perfuse the myocardial region subtended by the right coronary artery. Six patients scheduled to undergo elective coronary artery bypass surgery were evaluated with contrast echocardiography to determine the distribution of retrograde-delivered cardioplegia into the right ventricle. Sonicated Renografin-76 (Squibb Diagnostics, Princeton, NJ) was injected during retrograde delivery of cold crystalloid cardioplegia solution and continuous two-dimensional ultrasound imaging of the heart. On-line videodensitometric analysis was performed with a digital ultrasound system. The area under the curve and peak pixel intensity were determined for the anterior septum, the posterior septum, and the right ventricular free wall for each contrast injection. Recorded VHS videotape images of contrast-enhanced perfusion patterns were also reviewed and scored. On-line acoustic-densitometric analysis showed that right ventricular posterior and anterior septal peak pixel intensities were 4.8 +/- 3.2 and 7.3 +/- 1.5, respectively, compared with only 1.6 +/- 1.2 (p < or = 0.05) in the right ventricular free wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta.

In humans the glutathione S-transferase (GST) genes encode four classes of proteins (GST) important in the detoxification of reactive electrophiles. Recently, a gene deletion polymorphism was discovered within the GST class theta locus that leads to a functional deficiency in GST theta activity within circulating red blood cells. In this study we have examined the ethnic distribution of this polymorphism using a polymerase chain reaction (PCR)-based genotyping method. Five different ethnic groups were studied: North American Caucasians, African-Americans, Mexican-Americans, Chinese and Koreans. The prevalence of the null genotype was highest among Chinese (64.4%), followed by Koreans (60.2%), African-Americans (21.8%) and Caucasians (20.4%), whereas the prevalence was lowest among Mexican-Americans (9.7%). Interestingly, the prevalence of the deleted genotype in Caucasians differed significantly when 257 individuals drawn from a nation wide organization were compared with 185 people from the New England area (23.7 versus 15.7%, P < 0.05, chi 2 test). These results indicate that there are major differences in the prevalence of this trait attributable to ethnicity and that ethnic origin even among Caucasians should be considered in studies of gene-environment interaction involving this polymorphism.

Asian People↗

PubMed1995

Provocative chelation with DMSA and EDTA: evidence for differential access to lead storage sites.

OBJECTIVES--To validate a provocative chelation test with 2,3-dimercaptosuccinic acid (DMSA) by direct comparison with the standard ethylene diamine tetraacetic acid (EDTA) test in the same subjects; and to compare and contrast the predictors of lead excretion after DMSA with those after EDTA. A metal chelating agent given orally, DMSA may mobilise and enhance the excretion of lead from the storage sites in the body that are most directly relevant to the health effects of lead. A provocative chelation test with DMSA could thus have wide potential application in clinical care and epidemiological studies. METHODS--34 male lead workers in the Republic of Korea were given a single oral dose of 10 mg/kg DMSA, urine was collected over the next eight to 24 hours, and urine volume and urinary lead concentration determined at 0, 2, 4, 6, 8, and 24 hours. Either two weeks before or two weeks after the dose of DMSA 17 of these workers also received 1 g intravenous EDTA followed by an eight hour urine collection with fractionation at 0, 2, 4, 6, and 8 hours. RESULTS--Urinary lead concentration peaked at two hours after DMSA and four hours after EDTA. Lead excretion after DMSA was less than after EDTA, and cumulative excretion after DMSA plateaued at six to eight hours. The two hour and four hour cumulative lead excretions after DMSA were highly correlated with the eight hour total (r = 0.76 and 0.95). In multiple linear regression analyses, blood lead was found to be an important predictor of EDTA-chelatable lead, whereas urinary aminolevulinic acid (ALAU) was associated with DMSA-chelatable lead. Notably, lead excretion after DMSA was greatly increased if EDTA was given first. An earlier dose of EDTA also modified the relation between ALAU and DMSA-chelatable lead in that workers who received EDTA before DMSA showed a much steeper dose-response relation between these two measures. CONCLUSIONS--The predictors of lead excretion after DMSA and EDTA are different and an earlier dose of EDTA may increase lead excretion after a subsequent dose of DMSA. The results suggest that two hour or four hour cumulative lead excretion after DMSA may provide an estimate of lead in storage sites that are most directly relevant to the health effects of lead.

Adult↗

PubMed1995

Evaluation of lead exposure in workers at a lead-acid battery factory in Korea: with focus on activity of erythrocyte pyrimidine 5'-nucleotidase (P5N).

OBJECTIVE: To evaluate lead exposure among lead-acid battery workers in Korea, to evaluate in more detail the erythrocyte pyrimidine 5'-nucleotidase (P5N) test for lead exposure, and to evaluate the abnormal accumulation of erythrocyte pyrimidine nucleotides in the battery workers. METHODS: Activity of P5N and other biological variables were examined in 66 exposed workers in a lead-acid battery factory and in 26 non-exposed workers in Korea. RESULTS: At the factory the time-weighted average of 13 (72%) of 18 air samples for lead exceeded 0.05 (range 0.012-0.468) mg/m3. Blood lead concentration (PbB) in 39 of the 66 exposed workers was above 40 micrograms/dl, and the mean (SD) PbB in the exposed group was 45.7 (15.7) micrograms/dl. Compared with the nonexposed group, free erythrocyte protoporphyrin in the exposed group was significantly increased, whereas erythrocyte P5N activity and activity of erythrocyte delta-aminolevulinic acid dehydratase (ALAD) were significantly inhibited. Erythrocyte P5N activity had valid correlation biologically with PbB and with other biological variables, such as ALAD activity. In 28 exposed workers, the concentration of erythrocyte pyrimidine nucleotides (uridine 5'-diphosphate-glucose and cytidine 5'-triphosphate) correlated inversely with P5N activity and positively with PbB. CONCLUSIONS: These findings show that the depression of erythrocyte P5N activity by lead exposure results in the accumulation of erythrocyte pyrimidine nucleotides. In general, the standard analysis of PbB performed in laboratories around the world remains the most useful index of recent exposure. The results indicate that the erythrocyte P5N activity test provides supporting evidence of lead exposure and shows the effect of lead on nucleotide metabolism.

5'-Nucleotidase↗

PubMed1995

CD34 immunohistochemical staining of bone marrow biopsies in myelodysplastic syndromes.

Although it has been shown that the percentage of bone marrow blasts in myelodysplastic syndrome (MDS) constitute the only independent determinant of survival and progression to acute leukemia, the great variability in survival among patients with MDS of similar percentage of blasts has prompted us to investigate new objective, independent prognostic parameters for the selection of high-risk patients. It was suggested that CD34 antigen expression adversely affected the prognosis of acute myelogenous leukemia. However, no study has been published so far on clinical and prognostic significance of CD34 antigen expression in MDS. Bone marrow biopsies from 58 patients diagnosed as primary MDS were studied using QBEND/10, a monoclonal antibody which recognized the human progenitor CD34 antigen on routine aldehyde-fixed, paraffin-embedded samples. The high percentage of CD34-positive cells (above 3% of total bone marrow nucleated cells) was predominantly observed in cases with RAEB-T, CMML, and to a lesser degree in RAEB. But neither age, hemograms, bone marrow findings including percentage of blasts, ALIP, nor leukemic transformation correlated with the percentage of CD34-positive cells. The median actuarial survival time in the high positive group was significantly shorter (12.0 months) than that of the low group (30.0 months; p = 0.028). The high CD34 aggregate (> or = 3) was selectively found in cases with RAEB, RAEB-T, and CMML. The percentage of bone marrow blasts (p = 0.007) and ALIP (p = 0.030) significantly correlated with number of CD34 aggregates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Differential responses of CD34-positive acute myelogenous leukemic blasts to the costimulating effects of stem cell factor with GM-CSF and/or IL-3.

Stem cell factor (SCF), a c-kit ligand, has a preferential effect on the proliferation of several classes of immature hematopoietic progenitor cells in combination with GM-CSF or IL-3. To analyze the costimulatory role of SCF in leukemic growth, we investigated the effect of SCF in the presence of GM-CSF and/or IL-3 on isolated CD34-positive (CD34+) leukemic blasts from 15 patients with acute myelogenous leukemia (AML). Cultures of CD34+ cells from normal bone marrow were used as controls. When the proliferation of CD34+ AML blasts in the presence of GM-CSF and/or IL-3 were evaluated in vitro for the effects of SCF, two patterns emerged. In one pattern, CD34+ AML blasts responded with a significant increase in DNA synthesis and/or colony formation when SCF was used with GM-CSF and/or IL-3 relative to the growth with SCF alone; This result is consistent with those CD34+ bone marrow cells from normal donors. Six patients (40%) were included in this category. The addition of SCF as a single factor resulted in colony formation in all six of these cases. In the other pattern, nine of the patients (60%) had CD34+ leukemic cells whose growth with SCF plus either GM-CSF, IL-3, or GM-CSF+IL-3, was not significantly different from the growth noted in the presence of SCF alone. Among them seven cases that did not form colonies in response to SCF alone, and one case showing autocrine, background growth were included. In the six cases in which the costimulating effects of SCF were documented, CD34+ c-kit+ blasts comprised 50.5 +/- 18.7% of the CD34+ leukemic blasts-higher than 21.8 +/- 19.4% of cases in which the costimulating effect of SCF was not documented. In the cases showing high c-kit antigen expression (> or = 40%), SCF had a costimulatory effect in 71% (5/7) of the patients. In conclusion, our data indicate that CD34+ leukemic blasts from a good proportion of patients with AML did not respond to the costimulating effects of SCF in the presence of GM-CSF adn/or IL-3, in contrast to those CD34+ bone marrow cells from normal donors. The possible use of SCF for acute leukemia must await further cytogenetic and molecular studies, which should clarify the preferential costimulating role of SCF in normal hematopoiesis.

Antigens, CD↗

PubMed1995

Clinical significance of serum TSH in euthyroid patients with paroxysmal atrial fibrillation.

Atrial fibrillation may occur in patients with a variety of cardiovascular or chronic disease as well as in normal subjects. Many authors reported that atrial fibrillation occurs in patients with thyrotoxicosis. It is reported that a low serum thyrotrophin concentration in an asymptomatic person with normal serum thyroid hormone concentrations can be a independent risk factor for developing atrial fibrillation. But we focused on the significance of serum thyroid stimulating hormone (TSH) in the euthyroid patient with atrial fibrillation whose serum level of T3, T4, fT4, and even TSH were absolutely within normal range. On our results, there was no significant differences in age, sexual distribution, and left ventricular ejection fraction between the patients group of paroxysmal and chronic persistent atrial fibrillation (p > 0.05), but there was larger left atrial dimension (LAD) and more cases of rheumatic heart disease in the chronic persistent atrial fibrillation group and there was more cases of lone atrial fibrillation in the paroxysmal atrial fibrillation group (p < 0.05). There was no significant differences in serum levels of T3, T4, fT4 between paroxysmal and chronic persistent atrial fibrillation, but significantly lower serum TSH was found in patients with paroxysmal atrial fibrillation (p < 0.001), and these findings were more significant after the control of hemodynamic change (p < 0.001 vs p < 0.05). The discriminant value in serum TSH between the paroxysmal and chronic atrial fibrillation group was 1.568U/mL with about 76% of predictive power. There was significantly lower serum TSH in paroxysmal atrial fibrillation in all age groups (p < 0.05). There was a significantly higher prevalence of cerebral thromboembolic events in chronic persistent (27.7%) and disease-associated (15.0% atrial fibrillation than in the paroxysmal (3.3%) and lone (4.5%) atrial fibrillation group (p < 0.001). Therefore, we suggest that serum TSH below the serum concentration of 1.5U/mL can be a risk factor for developing atrial fibrillation when the serum level of T3, T4, fT4, and even TSH were within absolutely normal range.

Adult↗

PubMed1994

Primate antibody response to immunotoxin: serological and computer-aided analysis of epitopes on a truncated form of Pseudomonas exotoxin.

NLysPE38 is a 38-kDa derivative of Pseudomonas exotoxin (PE) in which domain Ia (amino acids 1 to 252) and part of domain Ib (365 to 380) are deleted and an 11-amino-acid N-terminal peptide is added. LMB-1 is an immunotoxin in which the monoclonal antibody B3 is coupled to NLysPE38 near its N terminus. LMB-7 is a single-chain immunotoxin in which the Fv fragment of B3 is fused to PE38. To identify the antigenic regions of PE38, 12 polyclonal serum samples from monkeys immunized with the immunotoxins LMB-1 (six monkeys) and LMB-7 (six monkeys) were tested for their reactivity to a panel of 120 synthetic, overlapping peptides representing the amino acid sequence of NLysPE38. The antibody responses to peptides were similar among the 12 serum specimens, identifying several major immunodominant B-cell epitopes. Predominant reactivity was seen in six locations: amino acids 272 to 287, 341 to 359, 504 to 516, 540 to 564, and 573 to 591 and the C-terminal amino acids 591 to 613. The sera did not react with approximately 75% of the peptides. Furthermore, a computer-aided analysis was done to predict the immunologically relevant areas and revealed the same antigenic regions defined by serum reactivity to peptides. Competition enzyme-linked immunosorbent assays and neutralization assays were performed with domain II, III, or III plus Ib of PE38 and confirmed the immunodominance of domain III. To analyze the role of specific amino acids in antibody binding, individual amino acids of PE38 with large accessible surface areas were altered by site-directed mutagenesis. These results also show that the predicted areas of immunogenicity agree with the reactivity of the anti-PE38 antibodies to peptides and to the mutants of PE.

ADP Ribose Transferases↗

PubMed1994

The relationship between immediate outcome after cardiac surgery, homogeneous cardioplegia delivery, and ejection fraction.

BACKGROUND: Optimal myocardial protection during cardiac surgery with ischemic arrest is predicated on among other variables, homogeneous cardioplegia distribution. Contrast echocardiography has been shown to provide information regarding the intramyocardial distribution of cardioplegia solution. To test the hypothesis that information regarding cardioplegia distribution derived from contrast echocardiography may be associated with immediate clinical outcome after cardiac surgery, data from 21 patients were examined retrospectively. METHODS: Contrast-enhanced cardioplegia distribution patterns of the left ventricle short axis view obtained with transesophageal echocardiography were examined off-line by four observers blinded to clinical outcome. Contrast effect was scored for eight equally divided myocardial segments (0 = no contrast, 1 = nonuniform contrast, 2 = uniform contrast, 3 = excessive contrast). The scores were then averaged between segments and between observers to generate an antegrade, a retrograde, and a combined global contrast score for each patient. RESULTS: Seventeen patients were separated from bypass without difficulty (group A) and 4 patients required sustained inotropic therapy or an intra-aortic balloon pump to facilitate separation from bypass (group B). As would be expected, group A patients had a higher average preoperative ejection fraction than did group B patients (60 percent +/- 14 vs 31 percent +/- 7, p < 0.01). In group A, however, for 4 of 17 patients (23 percent), low preoperative ejection fraction was not predictive of postoperative exogenous circulatory support requirements. Group A patients also had significantly higher antegrade (1.6 vs 1.2, p < 0.02), retrograde (1.7 vs 1.1, p < 0.02), and combined global contrast scores (1.7 vs 1.1, p < 0.01) than did group B patients. All patients with low preoperative ejection fraction and low intraoperative contrast scores required exogenous support to separate from cardiopulmonary bypass. CONCLUSION: Contrast echocardiography makes possible an evaluation of the intensity and distribution of contrast-enhanced cardioplegia delivery and we believe the efficacy of intraoperative myocardial protection. Although low preoperative ejection fraction is a known predictor of poor immediate postoperative outcome following cardiac surgery, not all patients with low preoperative ejection fractions require inotropic support postoperatively. Our results suggest that monitoring cardioplegia distribution with contrast echocardiography may offer insight for better patient stratification based on intraoperative myocardial protection in patients with low ejection fraction. We believe a more extensive evaluation of this relationship should be pursued in a prospective manner.

Aged↗

PubMed1993

Structure of the hormone binding domain of human beta 1 thyroid hormone nuclear receptor: is it an alpha/beta barrel?

To understand the structure of the hormone binding domain (HBD) of human beta 1 thyroid hormone nuclear receptor (h-TR beta 1), truncated h-TR beta 1 fragments, MD32 (M169-D456), KD29 (K201-D456), DD28 (D211-D456), KD25 (K235-D456), and KP28 (K201-P448), were analyzed by circular dichorism (CD). MD32 and KD29 show intense CD spectra with double minima at 222 and 208-210 nm, indicating the presence of extensive regions of alpha-helix. DD28 and KD25 have spectra which are reduced in intensity with minima around 215 nm, characteristic of a beta-sheet. The observed spectra are compatible with sequence analysis which predicts that HBD contains alternating stretches of alpha-helix and beta-strand. These extensive decreases in secondary structure in DD28 and KP28 in which the predicted first beta-strand or last alpha-helix was deleted, respectively, were accompanied by the loss of hormone binding activity. On the basis of these results, we suggest a new model for h-TR beta 1 consisting of the known DNA binding domain linked by an alpha-helical hinge to the HBD, with the tertiary structure of an alpha/beta barrel. The model is compatible with previous chemical and genetic studies on the structure of this protein.

Amino Acid Sequence↗

PubMed1993

Recombinant immunotoxins containing the VH or VL domain of monoclonal antibody B3 fused to Pseudomonas exotoxin.

We prepared recombinant immunotoxins in Escherichia coli in which the VH or VL domains of mAb B3 were fused to a truncated form of Pseudomonas exotoxin (PE) (PE38KDEL). mAb B3 binds to a carbohydrate Ag found on the surfaces of many types of cancers and only a few normal tissues. PE38KDEL is a 38-kDa form of PE (66 kDa) that is missing the cell-binding domain of PE and has the carboxyl end changed from REDLK to KDEL. We show that immunotoxins in which the H chain or the L chain V region is fused to PE38KDEL bind to and kill carcinoma cells containing the B3 Ag. B3 Ag-negative cells were not affected. The cytotoxicity of these molecules is between 20- and 100-fold less than B3(Fv)-immunotoxins, containing both the H and L chain V regions. The VL-containing toxin was more active than the VH-containing toxin, indicating that the L chain of mAb B3 probably contributes more to Ag-binding than the H chain. Refolding experiments show that B3(VL)-PE38KDEL aggregates less than the VH-derivative or than a single chain immunotoxin B3(Fv)-PE38KDEL, which contains both domains in a single chain form. Furthermore, in addition to monomers, active homodimers of B3(VH)- and B3(VL)-PE38KDEL were obtained from renaturation experiments. The VL-toxin dimers, which might have their binding regions arranged in a manner similar to Bence Jones proteins (L chain homodimers), were found to have almost the same cytotoxicity as the monomers, whereas the VH-toxin dimers had decreased cytotoxic activity.

ADP Ribose Transferases↗

PubMed1993

The effect of respiratory protection with biological monitoring on the health management of lead workers in a storage battery industry.

Respiratory protection with maintenance free respirator and regular biological monitoring with the measurement of zinc protoporphyrin for one year period not only made significant decreases of biological indices indicative of lead exposure (blood lead, delta-aminolevulinic acid in urine) in a storage battery workers, but also reduced the prevalence of lead related symptoms.

Aminolevulinic Acid↗

PubMed1993

Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus.

BACKGROUND: Endothelium-dependent vasodilation is abnormal in experimental models of diabetes mellitus. We postulated that abnormalities of endothelial function are also present in patients with insulin-dependent diabetes mellitus and may contribute to the pathogenesis of vascular disease in these individuals. METHODS AND RESULTS: Vascular reactivity was measured in the forearm resistance vessels of 15 patients with insulin-dependent diabetes mellitus and 16 age-matched normal subjects. No patient had hypertension or dyslipidemia. Each subject was pretreated with aspirin to inhibit endogenous production of prostanoids. Methacholine chloride (0.3 to 10 micrograms/min) was administered via the brachial artery to assess endothelium-dependent vasodilation. Sodium nitroprusside (0.3 to 10 micrograms/min) and verapamil (10 to 300 micrograms/min) were infused intra-arterially to assess endothelium-independent vasodilation; phenylephrine (0.3 to 3 micrograms/min) was administered to examine vasoconstrictor responsiveness. Forearm blood flow was determined by venous occlusion plethysmography, and dose-response curves were generated for each drug. Basal forearm blood flow in diabetic and normal subjects was comparable (2.6 +/- 0.2 versus 2.1 +/- 0.3 mL x 100 mL-1 x min-1, respectively; P = NS). The forearm vasodilative response to methacholine was less in diabetic than in normal subjects. At the highest dose of methacholine, the forearm blood flow increased 9.5 +/- 1.1 mL x 100 mL-1 x min-1 in diabetic subjects and 15.3 +/- 1.4 mL.100 mL-1 x min-1 in normal subjects (P < .01). The forearm blood flow responses to nitroprusside and verapamil and the forearm vasoconstrictor responses to phenylephrine were similar in diabetic and healthy subjects. In diabetic subjects, endothelium-dependent vasodilation correlated inversely with serum insulin concentration but not with glucose concentration, glycosylated hemoglobin, or duration of diabetes. CONCLUSIONS: Endothelium-dependent vasodilation is abnormal in forearm resistance vessels of patients with insulin-dependent diabetes mellitus. This abnormality may be relevant to the high prevalence of vascular disease that occurs in these individuals.

Adult↗

PubMed1993

Studies on IL-2 production and T-cell colony forming unit in patients with chronic renal failure.

To elucidate the nature of altered cellular immunity seen in patients with chronic renal failure, the values of interleukin-2 (IL-2), a kind of lymphokine, and T-cell colony forming units were measured in controls (N = 10), predialysis uremic patients (N = 14), patients undergoing chronic hemodialysis (HD, N = 11) and patients on continuous ambulatory peritoneal dialysis (CAPD, N = 9). Dialytic patients were selected as relatively stable cases receiving dialysis for more than 3 months. The duration of dialysis was 25.5 +/- 5.5 months in HD and 14.7 +/- 3.0 months in CAPD groups. The mean age was 30.3 years in the control, 36.1 years in the predialysis, 32.9 years in the HD and 41.1 years in the CAPD groups; all 4 groups showed male predominance. The serum creatinine concentration of each group was 1.2 +/- 0.1 mg/dl in the control, 14.1 +/- 0.9 mg/dl in predialysis, 13.5 +/- 1.3 mg/dl in HD and 14.7 +/- 0.9 mg/dl in CAPD groups. The level of IL-2 in the predialysis group was markedly lower compared to the control, HD and CAPD groups (as 3.1 +/- 0.8 unit vs. 8.8 +/- 2.2 unit, 11.8 +/- 3.0 unit and 14.9 +/- 3.4 unit, respectively, p < 0.05); the difference between the control and dialytic groups was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗