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Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 343 records · Page 19Linked to original sources
PubMed1999

Efficacy of anti-tumor necrosis factor-alpha antibody as an adjunctive therapy in experimental Escherichia coli meningitis in the newborn piglet.

This study was done to evaluate the efficacy of anti-tumor necrosis factor alpha (anti-TNF-alpha) antibody as an adjunctive therapy in neonatal bacterial meningitis. Newborn piglets were divided into three groups: 8 in the control group, 13 in the meningitis group (MG), and 10 in the meningitis with anti-TNF-alpha antibody group (AG). Meningitis was induced by intracisternal injection of 10(8) colony-forming units of Escherichia coli in 100 microl of saline. In the AG, 200 microl of anti-TNF-alpha antibody was also given intracisternally. In the AG, the elevated cerebrospinal fluid TNF-alpha level observed in the MG was completely abolished, and increased intracranial pressure, hypoglycorrhachia, and CSF pleocytosis observed in the MG were downmodulated. But blood, brain, and CSF lactate levels remained elevated in both MG and AG. Increased brain cell membrane lipid peroxidation products and decreased Na+,K+-ATPase activity observed in the MG were not attenuated in the AG. These results indicate that anti-TNF-alpha antibody was not particularly effective as an adjunctive therapy in attenuating acute inflammatory responses and ameliorating brain damage in neonatal bacterial meningitis.

Animals↗
PubMed1999

Surgical management of intractable epilepsy in children with hemophilia.

Intracranial hemorrhage occurs in 2-8% of patients with hemophilia and can result in neurologic sequelae including seizure disorders. There is a paucity of data concerning the surgical treatment of epilepsy in children with hemophilia. We review our experience with 2 children who developed medically refractory seizure disorders. Both children underwent hemispherotomy, at 18 months (case 1) and 13 years of age (case 2), respectively. Perioperative management included continuous factor replacement. Both children tolerated surgical intervention without complications or increased neurologic deficit. Case 2 showed a 90% reduction in seizure frequency, and case 1 is seizure free. Surgical management of intractable epilepsy in children with hemophilia is safe and effective.

Brain↗
PubMed1999

Depletion of pre beta 1LpA1 and LpA4 particles by mast cell chymase reduces cholesterol efflux from macrophage foam cells induced by plasma.

Exposure of the LpA1-containing particles present in HDL3 and plasma to a minimal degree of proteolysis by the neutral protease chymase from exocytosed rat mast cell granules (granule remnants) leads to a reduction in the high-affinity component of cholesterol efflux from macrophage foam cells. In this study, we demonstrate for the first time, a role for mast cell chymase in the depletion of the lipid-poor minor components of HDL that are specifically involved in reverse cholesterol transport as initial acceptors of cellular cholesterol. Thus, addition of proteolytically active granule remnants or human skin chymase to cholesterol-loaded macrophages of mouse or human origin incubated with human apoA1, ie, a system in which prebeta1LpA1 is generated, resulted in a sharp reduction in the high-affinity cholesterol efflux promoted by apoA1. As determined by nondenaturing 2-dimensional polyacrylamide gradient gel electrophoresis, the granule remnants effectively depleted the prebeta1LpA1, but not the alphaLpA1, in HDL3 and in plasma during incubation at 37 degrees C for <1 hour. Incubation of plasma with granule remnants for 1 hour also led to near disappearance of the LpA4-1 and LpA4-2 particles, but did not affect the distribution of the apoA2-containing lipoproteins present in the plasma. We conclude that the reduced ability of granule remnant-treated HDL3 and granule remnant-treated plasma to induce cholesterol efflux from macrophage foam cells is caused by selective depletion by mast cell chymase of quantitatively minor A1- and A4-containing subpopulations of HDL. Because these particles, ie, prebeta1LpA1 and LpA4, are efficient acceptors of cholesterol from cell surfaces, their depletion by mast cells may block the initiation of reverse cholesterol transport in vivo and thereby favor foam cell formation in the arterial intima, the site of atherogenesis.

Animals↗
PubMed1999

The growth-related, translationally controlled protein P23 has properties of a tubulin binding protein and associates transiently with microtubules during the cell cycle.

The translationally controlled protein P23 was discovered by the early induction of its rate of synthesis after mitogenic stimulation of mouse fibroblasts. P23 is expressed in almost all mammalian tissues and it is highly conserved between animals, plants and yeast. Based on its amino acid sequence, P23 cannot be attributed to any known protein family, and its cellular function remains to be elucidated. Here, we present evidence that P23 has properties of a tubulin binding protein that associates with microtubules in a cell cycle-dependent manner. (1) P23 is a cytoplasmic protein that occurs in complexes of 100-150 kDa, and part of P23 can be immunoprecipitated from HeLa cell extracts with anti-tubulin antibodies. (2) In immunolocalisation experiments we find P23 associated with microtubules during G1, S, G2 and early M phase of the cell cycle. At metaphase, P23 is also bound to the mitotic spindle, and it is detached from the spindle during metaphase-anaphase transition. (3) A GST-P23 fusion protein interacts with alpha- and beta-tubulin, and recombinant P23 binds to taxol-stabilised microtubules in vitro. The tubulin binding domain of P23 was identified by mutational analysis; it shows similarity to part of the tubulin binding domain of the microtubule-associated protein MAP-1B. (4) Overexpression of P23 results in cell growth retardation and in alterations of cell morphology. Moreover, elevation of P23 levels leads to microtubule rearrangements and to an increase in microtubule mass and stability.

3T3 Cells↗
PubMed1999

Employee drinking practices and work performance.

OBJECTIVE: The purpose of this study was to examine the independent effects of a variety of drinking indicators on self-reported work performance. METHOD: Data from a cross-sectional mailed survey (response rate = 71%) of managers, supervisors and workers (N = 6,540) at 16 worksites were analyzed. Average daily volume was computed from frequency and usual quantity reports. Drinking on the job included drinking during any of six workday situations. The CAGE was used to indicate alcohol dependence. Employees were also asked how frequently they drank to get high or drunk. Work performance was measured through a series of questions about work problems during the prior year. The number of times respondents experienced work performance problems was regressed on the four drinking measures, and a variety of demographic characteristics, job characteristics and life circumstances that might also negatively affect work performance. RESULTS: The frequency of self-reported work performance problems increased, generally, with all four drinking measures. In a multivariate model that controlled for a number of demographics, job characteristics and life-situations, average daily volume was no longer significantly associated with work performance but the other three drinking measures were. Interestingly, although moderate-heavy and heavy drinkers reported more work performance problems than very light, light, or moderate drinkers, the lower-level-drinking employees, since they were more plentiful, accounted for a larger proportion of work performance problems than did the heavier drinking groups. CONCLUSIONS: Employers should develop clear policies limiting drinking on the job and, in addition to employee assistance programs for problem drinkers, should develop worksite educational interventions aimed at informing all employees about the relationship between drinking behaviors and work performance.

Absenteeism↗
PubMed1999

Alcoholics anonymous affiliation at treatment intake among white and black Americans.

OBJECTIVE: Black Americans are overrepresented in the public alcohol treatment system, but may be less likely to use informal services such as Alcoholics Anonymous (AA). Some commentators perceive AA as a white, middle-class organization that is unlikely to appeal to blacks. This epidemiological study considers prior attendance and engagement in AA among 791 black and white men and women entering treatment in public, private and HMO substance abuse programs. METHOD: Clients were interviewed in-person within the first 3 days of inpatient treatment or the first 3 weeks of outpatient treatment. RESULTS: Black clients dominate public detoxification programs and report more drug and employment problems than whites (who report more family problems). Those with prior treatment experiences and those reporting they had gone to AA as part of treatment reported overall higher rates of AA affiliation, with blacks more likely to say they felt like a member of AA (64% vs 54% of whites), had a spiritual awakening as a result of AA (38% vs 27%) and had done service at AA meetings in the last year (48% vs 37%); whites were more likely to have had a sponsor (23% vs 14%) and to have read program literature (77% vs 67%). CONCLUSIONS: Controlling for other effects such as prior inpatient or outpatient treatment, blacks are about twice as likely as whites to report having attended AA as part of treatment (OR = 1.70). More research is needed to understand referral pathways to AA among blacks, and the differential effect this may have on sustained participation in AA and on long-term sobriety.

Adult↗
PubMed1999

Transplantation of autologous peripheral blood progenitor cells procured after high-dose cytarabine-based consolidation chemotherapy for adults with secondary acute myelogenous leukemia in first remission.

Patients with acute myelogenous leukemia secondary to an antecedent hematologic disturbance or cytotoxic chemotherapy are considered to have a very low likelihood of leukemia-free survival regardless of the form of post-remission therapy. The purpose of this study is to evaluate, on the basis of intention to treat, the feasibility and efficacy of high-dose cytarabine/anthracycline consolidation chemotherapy followed by autologous transplantation of chemotherapy/rHuG-CSF-mobilized peripheral blood progenitor cells for seventeen adult patients (median age 63, range 27 to 68) with secondary acute myelogenous leukemia in first remission. Ten eligible patients underwent autologous transplantation of peripheral blood progenitor cells procured following high-dose cytarabine/mitoxantrone consolidation chemotherapy used as a method of in vivo purging. A median of 5 collections (range 2 to 13) were required to procure a median of 9.27 x 10(8) total mononuclear cells/kg (range 2.35 to 21.44 x 10(8) per kg). The median number of CD34-positive progenitor cells was 1.18 x 10(6) kg (range 0.34 to 30.9 x 10(6) kg). After preparative conditioning with 11.25 Gy total body radiation and cyclophosphamide (120 mg/kg) and autologous transplantation, the median time to neutrophil and platelet recovery were 18 days (range 12 to 29 days) and 25 days (range 8 to 158+ days), respectively. After a median follow-up for surviving patients of 33.4 months (range 7.5 to 54 months), 9 of 17 patients (53%) remain alive with 7 in continued first remission. The median remission duration is 13 months (3 to 53 months) and actuarial leukemia-free survival at 3 years is 51+/-25%. Toxicity of autologous peripheral blood progenitor cell transplant included serious liver and pulmonary toxicity in 2 and 1 patient, respectively. Our results demonstrate that a postremission program of high-dose cytarabine-based consolidation chemotherapy followed by autologous transplantation of chemotherapy-mobilized peripheral blood progenitor cells is feasible for patients with secondary acute myelogenous leukemia producing prolonged leukemia-free survival with minimal toxicity.

Adult↗
PubMed1999

Expression of Th1 and Th2 type cytokines responding to HBsAg and HBxAg in chronic hepatitis B patients.

The cytokine pattern on viral antigen recognition is believed to exert a profound influence on the resolution of viral infections and viral clearance. This study was initiated to investigate whether a cytokine imbalance oriented toward Th2 type response plays a role in chronic hepatitis B. Cytokine profiles of peripheral blood mononuclear cells associated with chronic hepatitis B were analysed by RT-PCR. Upon HBsAg stimulation, expression of IFN-gamma, IL-2, IL-4, and IL-10 was detected in 41%, 8%, 41%, and 50% of the patients, respectively. Among these cytokines, the expression of IFN-gamma was associated with high levels of serum AST/ALT. However, we could not prove that Th2 type cytokines had a protective effect on hepatocytes. Upon HBxAg stimulation, there was no recognizable association of cytokine patterns with AST/ALT levels. In conclusion, production of a Th1 cytokine, IFN-gamma, by HBsAg-reactive cells was associated with hepatocyte damage in chronic hepatitis B, while no counteracting effect of Th2 cytokines produced by those cells was observed.

Cytokines↗
PubMed1999

Long-lasting sonographic and histopathological findings in cured clonorchiasis of rabbits.

To ascertain residual sonographic and histopathological findings of clonorchiasis after treatment, the present study evaluated sonographic findings in rabbits which were infected with 500 metacercariae of C. sinensis every 6 months for 18 months after treatment with praziquantel. The sonographic findings were analyzed in terms of intrahepatic bile duct dilatation and periductal echogenicity, and histopathological findings were observed after the last sonographic examination. Compared with the sonographic findings before treatment, dilatation of the intrahepatic bile ducts became mild to some degree in four of the seven cases and increased periductal echogenicity resolved in four of them. The histopathological specimens after 18 months showed that periductal inflammation has almost resolved but moderate dilatation of the intrahepatic ducts and mucosal hyperplasia persisted. The periductal fibrosis minimally resolved. The long-lasting sonographic findings in cured clonorchiasis make sonography less specific.

Animals↗
PubMed1999

Usefulness of IgG4 subclass antibodies for diagnosis of human clonorchiasis.

The present study analyzed serum IgG subclass antibody reaction to major antigenic bands of Clonorchis sinensis to investigate improvement of its serodiagnosis. Of the four subclass antibodies, IgG1 and IgG2 antibodies were produced but not specific, IgG3 antibody was least produced, and IgG4 antibody was prominent and specific. The serum IgG antibody reaction to any of 43-50, 34-37, 26-28, and 8 kDa bands was found in 65.5% of 168 egg positive cases while IgG4 antibody reaction was found in 22.0% of them. The positive rates of IgG and IgG4 antibodies were directly correlated with the intensity of infection. All of the sera from heavily infected cases over EPG 5,000 showed positive reaction for specific IgG and IgG4 antibodies. The specific serum IgG4 antibody disappeared within 6 months after treatment. The bands of 35 kDa and 67 kDa cross-reacted with IgG antibodies but not with IgG4 antibodies in sera of other trematode infections. The present findings suggest that serum IgG4 antibody reaction to 8 kDa band is specific but not sensitive. Any method to increase its sensitivity is required for improved serodiagnosis.

Animals↗
PubMed1999

The relationship between submaximal activity of the lumbar extensor muscles and lumbar posteroanterior stiffness.

BACKGROUND AND PURPOSE: Some patients with low back pain are thought to have increased lumbar posteroanterior (PA) stiffness. Increased activity of the lumbar extensors could contribute to this stiffness. This activity may be seen when a PA force is applied and is thought to represent much less force than occurs with a maximal voluntary contraction (MVC). Although MVCs of the lumbar extensors are known to increase lumbar PA stiffness, the effect of small amounts of voluntary contraction is not known. In this study, the effect of varying amounts of voluntary isometric muscle activity of the lumbar extensors on lumbar PA stiffness was examined. SUBJECTS: Twenty subjects without low back pain, aged 26 to 45 years (X=34, SD=5.6), participated in the study. METHODS: Subjects were asked to perform an isometric MVC of their lumbar extensor muscles with their pelvis fixed by exerting a force against a steel plate located over their T4 spinous process. They were then asked to perform contractions generating force equivalent to 0%, 10%, 30%, 50%, and 100% of that obtained with an MVC. Posteroanterior stiffness at L4 was measured during these contractions. RESULTS: A Friedman one-way analysis of variance for repeated measures demonstrated a difference in PA stiffness among all levels of muscle activity. CONCLUSION AND DISCUSSION: Voluntary contraction of the lumbar extensor muscles will result in an increase in lumbar PA stiffness even at low levels of activity.

Adult↗
PubMed1999

Effect of aspirin on prostaglandin E2 formation and transforming growth factor alpha expression in human rectal mucosa from individuals with a history of adenomatous polyps of the colon.

Colorectal cancer is the second-most frequent cause of cancer mortality in the United States. Human epidemiology and laboratory studies indicate that aspirin may be an effective colorectal cancer chemopreventive agent. This study was designed to determine whether treatment with 81 mg of aspirin per day for 3 months would alter two putative surrogate end point biomarkers of chemoprevention of colorectal cancer [i.e., mucosal prostaglandin E2 (PGE2) formation and transforming growth factor alpha (TGF-alpha) expression] in normal-appearing rectal mucosa from individuals with a history of adenomatous polyps. Rectal biopsies were obtained by flexible sigmoidoscopy at three sequential time points: (a) after a 1-month placebo run-in period (baseline), (b) after 3 months of ingesting 81 mg of aspirin (as a single tablet) once per day, and (c) after 3 months of ingesting a placebo tablet once per day (washout period). Daily aspirin significantly suppressed PGE2 formation, but this significant suppression was completely reversed when aspirin was withdrawn. The extent of TGF-alpha staining in rectal crypts was also reduced significantly (P = 0.039) by daily aspirin. After a 3-month placebo-washout period, however, the mean extent of TGF-alpha staining was not significantly different from either baseline or the aspirin time point. Thus, 81 mg of aspirin daily significantly reduced rectal mucosal PGE2 formation and TGF-alpha expression in patients with a history of adenomatous polyps. These putative surrogate end point biomarkers may be useful intermediate end points in future colorectal cancer chemoprevention trials.

Adenomatous Polyps↗
PubMed1999

The role of base excision repair in the repair of DNA adducts formed by a series of nitrogen mustard-containing analogues of distamycin of increasing binding site size.

The role of base excision repair in the repair of alkylation damage produced by a series of sequence specific oligopyrrole-containing analogues of distamycin A that tether benzoic acid mustard (BAM) has been examined. Whereas BAM alkylates and cross-links in the major groove of DNA, attachment to pyrrole units produces monoalkylations in the minor groove of DNA at AT tracts. Both sequence specificity of alkylation and cytotoxicity increase from one to three attached pyrrole units (compounds 1-3), and with 3 alkylation is selective for purine-N3 in the sequence 5'-TTTTGPu (where Pu = guanine or adenine). In a model bacterial (Escherichia coli) system repair of the sequence specific minor groove alkylations produced by 2 and 3 does not appear to involve BER, since neither a formamidopyrimidine-DNA glycosylase repair deficient E. coli mutant (BH 20, fpg- mutant) nor a 3-methyladenine-DNA glycosylase repair deficient mutant (GC 4803, tag-alkA- mutant) showed increased cytotoxicity to 2 or 3 compared with the wild type, AB 1157. The monopyrrole compound 1 was, however, approximately 4-fold more cytotoxic to the GC 4803 mutant compared with wild type and BH 20, suggesting a role for the 3-methyladenine-DNA glycosylase in the recognition and excision of the adducts formed by 1. In contrast, increased sensitivity (> 10-fold) was observed for the conventional nitrogen mustard BAM in the BH 20 strain, suggesting a role for the formamidopyrimidine-DNA glycosylase in the repair of the lesions produced by the agent. In a cell-free system the E. coli 3-methyladenine-DNA glycosylase (AlkA) was shown to remove alkylations at 5'-TTTTGPu sequences. However, the efficiency in removing the adducts formed by the oligopyrrole compounds decreased dramatically from compound 1 to compound 3. Increasing the size of the DNA adduct formed in the minor groove therefore decreased the efficiency of recognition and removal of the adduct by the DNA glycosylase.

Antineoplastic Agents, Alkylating↗
PubMed1999

Economic impact of automated primary screening for cervical cancer.

OBJECTIVE: To construct a markovian model to project the marginal cost of the AutoPap System as compared to manual cervical cytologic screening. STUDY DESIGN: Data from a clinical trial and published literature were entered into a seven-state markovian decision-analytic model to estimate the marginal cost per year of life saved that could be attributed to changes in primary screening technology. RESULTS: Annual screening with AutoPap produced a meaningful increase in life expectancy of 32.1 days relative to manual screening at a marginal savings of $628 per person (or a marginal savings of $7,144 per life-year saved). Less frequent screening yielded lower positive savings. CONCLUSION: Automated screening for cervical cancer has the potential to significantly improve health care outcomes and reduce cost.

Adolescent↗
PubMed1999

Skin necrosis induced by extravasation of glycerol-containing peripheral parenteral nutrition formulation.

Administration of parenteral nutrition (PN) via a peripheral vein has gained support over the last decade due to serious complications associated with central venous catheterization. Extravasation and tissue necrosis have been reported with both peripheral and central dextrose-containing PN formulations. The following case report represents the first documented case of skin necrosis due to extravasation of a glycerol-containing PN formulation. Our patient's condition resolved with local therapy such as elevation of the affected extremity and cold compresses. Routine evaluation of proper catheter placement is recommended to prevent this serious morbid event, while various treatment recommendations are outlined for severe injuries that do not respond to general measures such as cold compresses.

Aged↗
PubMed1999

A 40-kDa NF1-like protein, not YY1, binds to the rat p53 promoter for transactivation in various rat organs.

Two recognition motifs of a 40-kDa NF1-like protein were previously identified in the rat p53 promoter. One is located between -296 and -312 (NF1-like element 1) and the other between -195 and -219 (NF1-like element 2). The latter one was also identified as a NF1/YY1 recognition motif in the human p53 promoter. NF1 or YY1 binds to the motif and regulates the expression of the human p53 gene in a tissue-specific manner. In this study, we investigated the binding protein for NF1-like element 2 in various rat tissues. Unlike the human p53 transcription, an NF1-like protein, not YY1, bound to the motif in every tested tissue: thymus, kidney, and spleen. In vitro transcription assay also confirmed that the NF1-like protein regulated the p53 transcription in rat spleen, although the human p53 transcription was regulated by YY1 in that organ. The molecular mass of the binding protein was determined to be 40 kDa, which was the same as that of the NF1-like protein identified in liver. Therefore, the 40-kDa NF1-like protein may be a universal transcription regulator for the rat p53 gene.

Animals↗