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Biomedical subjects

M L Lee

Publications and source records attributed to M L Lee.

At least 145 records · Page 8Linked to original sources

Mosaic ring chromosome 13 analyzed by fluorescence in situ hybridization: report of a case.

A five-year-old boy with psychomotor retardation, microcephaly, bilateral cataracts, hearing impairment and hypospadia with microphallus was found to have multiple cell lines from peripheral blood: 46,XY/46,XY, -13,+r(13)/46, Xy, -13, +dic r(13) in the ratio of 35%/61%/4% by trypsin-Giemsa, and C-bandings. Using fluorescence in situ hybridization (FISH) with biotin-labeled alpha-satellite probe (D21Z1/D13Z1) and fluorescence staining (FITC), we confirmed that the ring originated from chromosome 13. To elucidate changes in the chromosome ends in the ring originated from chromosome 13. To elucidate changes in the chromosome ends in the ring formation, we used human telomere-specific probes for FISH study; it showed an absence of telomeres on the ring chromosome, although Ag-NOR staining was positive. These findings yielded different breaking points on the ends of both the short and long arms of chromosome 13 from those reported in the literature.

Abnormalities, Multiple↗

Ticlopidine: a new platelet aggregation inhibitor.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of ticlopidine are reviewed. Ticlopidine appears to inhibit platelet aggregation induced by adenosine diphosphate. Ticlopidine hydrochloride is rapidly absorbed after oral administration, and maximum antiplatelet effects occur one to three hours after the dose. In multicenter, randomized, double-blind trials, ticlopidine was more effective than aspirin or placebo in preventing stroke, myocardial infarction, or death caused by vascular events. Ticlopidine was more effective than aspirin in preventing recurrent transient ischemic attacks after six months of therapy. Ticlopidine has also been used to prevent occlusion and improve patency of aortocoronary bypass grafts, to prevent ischemic ulcers in patients with chronic arterial occlusive disease, and to slow the progression of diabetic microangiopathy. The most serious adverse effect, neutropenia, occurred in about 1% of patients. The most frequently reported adverse effects are diarrhea, nausea, vomiting, and abdominal cramps. Ticlopidine is indicated for reducing the risk of thrombotic stroke in patients who have experienced a minor stroke, transient ischemic attack, or completed thrombotic stroke. The recommended dosage is 500 mg/day in two divided doses taken with food. Ticlopidine is an alternative agent for the primary and secondary prevention of stroke. Because of the risk of neutropenia and agranulocytosis and the high cost of therapy, ticlopidine should be reserved for patients who are intolerant of or lack benefit from aspirin.

Animals↗

4 Beta- and 4 alpha-12-O-tetradecanoylphorbol-13-acetate elicit arachidonate release from epidermal cells through different mechanisms.

There is substantial evidence that the tumor promoter 4 beta-12-O-tetradecanoylphorbol-13-acetate (TPA) elicits enhanced arachidonic acid release and its metabolism to prostaglandins and lipoxygenase products in many cell types. The goal of this study was to determine whether 4 alpha-12-O-tetradecanoylphorbol-13-acetate (4 alpha TPA), a stereoisomer of TPA, can induce arachidonic acid release and whether it is by the same mechanism as release induced by TPA. The finding that 10 micrograms/ml 4 alpha TPA produces a response comparable with 1 microgram/ml TPA and with similar kinetics was unexpected. The mechanism mediating the TPA response appears to be the activation of protein kinase C (PKC), which subsequently results in phospholipase A2 activation. This is suggested by the observation that TPA-induced arachidonate release is inhibited 65% by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), an inhibitor of PKC and that TPA completely down-regulates PKC. In addition, down-regulation or depletion of PKC by prior treatment with TPA results in a 75% loss of response to a second TPA treatment. In vitro activation of partially purified PKC could be demonstrated for TPA but not 4 alpha TPA. 4 alpha TPA thus appears to induce the release of arachidonate by a different but unknown mechanism. The 4 alpha TPA effect is not significantly reduced by the PKC inhibitor H-7, and no evidence of PKC activation or down-regulation was observed. Additionally, 4 alpha TPA is unable to "down-regulate" arachidonate release when the two-treatment protocol is used and the down-regulation of PKC by TPA has little effect on 4 alpha TPA-induced arachidonate release. Cycloheximide inhibited TPA-induced arachidonate release by 80% and 4 alpha TPA-induced release by 50%, indicating a partial requirement for protein synthesis for both phorbol esters. Actinomycin D, on the other hand, inhibited the TPA response by 70%, but enhanced the 4 alpha TPA response by 169%. When used at 10- or 100-micrograms doses, 4 alpha TPA was found to lack activity with respect to ornithine decarboxylase induction, oxidant production, hyperplasia, inflammation, and tumor promotion, suggesting that arachidonate release is not sufficient to induce these events. This may be related to the observation that with TPA the extent of arachidonate metabolism to prostaglandin E2 is four- to fivefold greater than occurred with 4 alpha TPA, even under conditions of equivalent arachidonate release.

Animals↗

Effects of type of dietary fat on phorbol ester-elicited tumor promotion and other events in mouse skin.

Based on the biological activity of arachidonic acid metabolites, we hypothesized that alterations in the consumption of linoleic acid, the precursor to arachidonic acid, would result in a modification in tumor development when fed during the tumor promotion stage of the mouse skin initiation-promotion model. The effects of seven different levels of dietary linoleic acid (LA), supplied as corn oil in a 15% fat diet, on the incidence and rate of papilloma and carcinoma development were determined. SENCAR mice were placed on one of the experimental diets, containing 1.0, 3.6, 6.0, 7.9, 9.9, 12.5, or 15.0% corn oil, 1 week after initiation with 10 nmol of 7,12-dimethylbenz(a)anthracene and 3 weeks prior to the start of twice weekly promotion with 1 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA). At 15 weeks of TPA treatment there were significant differences in papilloma number among diet groups, such that an inverse correlation (r = 0.92) was observed between tumor number and level of corn oil; the lowest corn oil diet group had an average of 11.7 tumors/mouse, while the highest corn oil group had 5.4 tumors/mouse. However, there was little difference in tumor incidence among diet groups. A general relationship between diet and carcinoma incidence was also found, such that the highest corn oil diet group had the lowest carcinoma incidence. In an experiment performed with DBA/2 mice, the average number of papillomas/mouse at 17 weeks was 4.5 (1.0% corn oil), 5.6 (7.9%) corn oil), and 2.3 (15.0% corn oil). Papilloma incidence was also affected by diet, with a 79% incidence for the 15.0% corn oil and an incidence of 93% for the 1.0% corn oil group. analyses of the fatty acid composition of epidermal phospholipids in mice fed the experimental diets reflected the dietary LA levels, in that an accumulation of phospholipid LA, accompanied by an overall decrease in arachidonic acid, occurred with increasing dietary corn oil. In spite of the high membrane levels of LA, no measurable amount of epidermal conjugated dienes of LA could be detected. Epidermal prostaglandin E2 levels in acetone-treated mice were similar for all diet groups (approximately 3 pg/micrograms DNA). However, 6 h after topical application with 4 micrograms of TPA, prostaglandin E2 levels were elevated 5- to 10-fold; an inverse correlation (P less than 0.05) was seen with increasing dietary LA, although the concordance with decreased phospholipid arachidonic acid was not strong.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗

The problem of therapeutic equivalence with paired qualitative data: an example from a clinical trial using haemophiliacs with an inhibitor to factor VIII.

The problem of demonstrating the equivalence of two treatments or drugs occurs fairly frequently in medicine, but is quite often misformulated. The common error is to assume equivalence is demonstrated if the usual null hypothesis of no difference is not rejected, which ignores the potential of a substantial beta-error. We describe here two procedures for testing equivalence when the data are paired and dichotomous, and provide sample size formulas. We give an example based on a clinical trial of haemophiliacs with inhibitor to Factor VIII.

Antibodies↗

Antepartum cultures for Ureaplasma urealyticum are not useful in predicting pregnancy outcome. The Vaginal Infections and Prematurity Study Group.

To test the hypothesis that genital colonization with Ureaplasma urealyticum would predict adverse pregnancy outcome, 4934 women from five medical centers were evaluated for vaginal colonization with U. urealyticum between 23 and 26 weeks' gestation and followed up to delivery. U. urealyticum colonization was associated with maternal age, parity, racial-ethnic group, martial status, income, education, smoking, number of sexual partners, and colonization with Trichomonas vaginalis, Mycoplasma hominis, and bacterial vaginosis. After adjustment for medical and sociodemographic factors in a multivariate analysis, there was no difference in the mean birth weight or proportion of low-birth-weight infants delivered by women who carried U. urealyticum and those who did not. U. urealyticum colonization at 23 to 26 weeks was not associated with preterm rupture of membranes, preterm labor, or preterm delivery. A positive vaginal culture for U. urealyticum in midgestation does not predict those women at risk for preterm labor, preterm delivery, preterm premature rupture of membranes, or delivery of a low-birth-weight infant.

Adolescent↗

Analysis of prostaglandins in aqueous solutions by supercritical fluid extraction and chromatography.

Trace amounts of prostaglandins (PGs) were selectively analysed without derivatization using supercritical fluid extraction (SFE) and open tubular column supercritical fluid chromatography (SFC). The specific compounds studied were prostaglandin F2 alpha (PGF2 alpha), esters of PGF2 alpha, prostaglandin F1 alpha) and prostaglandin E2 (PGE2). An open tubular column was used with carbon dioxide as the mobile phase and with universal flame ionization detection. Samples were introduced into the column by direct injection using a 1-microliter sample loop or by SFE with solute focusing. The 11 standard compounds were effectively separated within 35 min using a density program at constant temperature. The minimum detectable quantity (signal-to-noise ratio = 3) using the direct injection method was 9 ng for 15-propionate PGF2 alpha isopropyl ester. Using the extraction method, the sample size in the extraction cell was increased to 100 microliters, which made it possible to analyse compounds that were present in low concentrations. Aqueous PG samples were extracted from adsorbents onto which the samples had been loaded.

Chromatography, Liquid↗

Vaginal Bacteroides species are associated with an increased rate of preterm delivery among women in preterm labor.

The relationship of high concentrations of vaginal microorganisms with an increased rate of preterm delivery (less than or equal to 34 weeks) among women in preterm labor was evaluated. Quantitative vaginal cultures were obtained from 211 women in preterm labor between gestational ages of 22 and 34 completed weeks. Preterm delivery occurred in 139 (66%). The rate of preterm delivery was determined by Cox proportional hazards models. Women with greater than 10(7) cfu/ml of vaginal fluid of facultative lactobacilli had a 40% decreased rate of preterm delivery (rate ratio [RR] = 0.6, 95% confidence interval (CI) = 0.4-0.9). An increased rate of preterm delivery occurred among women with Bacteroides bivius at concentrations of greater than 10(4) cfu/ml (RR = 2.0, 95% CI = 1.4-2.9) and Bacteroides fragilis (RR = 1.7, 95% CI = 1.0-2.8). Other microorganisms, including Gardernella vaginalis, the genital mycoplasmas, group B streptococci, Escherichia coli, and Peptostreptococcus species, were not associated with an increased rate of preterm delivery for women in preterm labor.

Adolescent↗

Survey of Australian isotretinoin prescribing.

In Australia, dermatologists have been designated as the sole prescribers of isotretinoin and thus we are in a unique position to audit national usage of the drug. Questionnaires were sent by the Australasian College of Dermatologists to all 204 practising Fellows in Australia. The aim was to study the number and type of patients treated with isotretinoin, the manner in which the drug is prescribed, adverse reactions and the number of pregnancies occurring during and after treatment. Judging from the 85% of questionnaires which were returned, isotretinoin is an effective and well-tolerated drug for the treatment of severe nodulocystic acne. In the five years that isotretinoin has been used in Australia, 11 pregnancies while taking the drug were reported. These pregnancies occurred despite exhaustive counselling by dermatologists and the patients being fully aware of the risks to the fetus and the need for adequate contraceptive measures. With one exception, all agreed to have a therapeutic abortion. There were two reports of congenital abnormalities after cessation of treatment, neither of which were thought to be related to isotretinoin. In several regions where a dermatologist is not available, a specialist physician may prescribe isotretinoin according to State Health regulations.

Acne Vulgaris↗

Isotretinoin: cost-benefit study.

Isotretinoin is a well-established, effective treatment for severe nodulocystic acne. An important consideration which may limit the prescription of isotretinoin is its cost. Based on a literature review, we have compared isotretinoin with the conventional combination of antibiotics and topical therapies for the treatment of severe nodulocystic acne in terms of cost and benefit. Our results show that when duration of treatment is considered, isotretinoin is cheaper and significantly more effective.

Acne Vulgaris↗

The pharmacokinetics of total IgG, IgG subclasses, and type specific antibodies in immunodeficient patients.

The advent of immunoglobulin concentrates suitable for intravenous administration has greatly improved the clinical management of patients with a primary immunodeficiency syndrome. However, proper treatment requires understanding of the pharmacokinetics of the infused IgG and its components. We review here the work that has been conducted in this area. In particular, two studies have shown that these concentrates have adequate catabolic properties with regards to total IgG, IgG subclasses, and specific antibodies. We conclude that careful evaluation of the pharmacokinetics of a given IgG preparation is necessary in order to determine an appropriate treatment regimen.

Female↗

Output and inflation components of medical care and other spending changes.

From 1965 to 1990, spending on medical care rose from 5.9 to 12.2 percent of gross national product. This rise was the consequence of greatly expanded government and government subsidized private insurance coverage operating in an environment where payments for insured care by and large covered whatever costs were incurred. As a result, the personal consumption of medical care experienced both output and price average growth rates strikingly above economywide norms. Indeed, the output growth rate in this sector rivaled growth in several goods sectors with greatly expanded supplies. However, whereas goods in the latter sectors have become more accessible through lower relative prices, consumers with insufficient insurance coverage are being crowded out of the market for medical care by higher relative prices.

Health Expenditures↗

Amoxicillin treatment of bacterial vaginosis during pregnancy.

The purpose of this investigation was to evaluate the efficacy of amoxicillin for treatment of bacterial vaginosis during pregnancy. The diagnosis of bacterial vaginosis was established by clinical examination and microscopic examination of a Gram stain and saline preparation of vaginal secretions. In a double-blind, randomized manner, 108 patients at 15-25 weeks' gestation were assigned to treatment with oral amoxicillin, 500 mg three times daily for 14 days, or placebo. Patients were evaluated 2 weeks after treatment, at 34-36 weeks' gestation, and at delivery. There were no significant differences between the two groups with respect to any clinical or microbiologic measure of treatment outcome. There were also no significant differences in the frequency of obstetric complications. We conclude that amoxicillin is not effective therapy for bacterial vaginosis in pregnant women.

Amoxicillin↗

A new approach to the computer-assisted quantitative analysis of nuclear shape.

In recent years, researchers have explored the use of computer-assisted morphometric analysis to evaluate nuclear shape. Most of these studies use nuclear shape factors which are based on circumference/surface measurement ratios, such as variations of the nuclear contour index, the form factor, and the nuclear roundness factor. Here we present a new method for the objective evaluation of nuclear shape, involving a simple computer-assisted determination of nuclear area (N) divided by the area of a rectangular figure (F) with sides tangent to the nuclear margin and parallel to the frame of a video monitor. Following calculation of N/F for individual nuclei, our method generates statistical parameters for quantitating nuclear irregularity directly at the population level: the mean N/F ratio; standard deviation; and coefficient of variation. Our use of surface/surface measurement ratios makes our method independent of both magnification and nuclear size. Our method is applied first to normal lymphocytes and neutrophils to manifest the parameters for nuclear irregularity which are generated by our method. The sensitivity of our method is demonstrated using lymphoblasts from patients with acute lymphoblastic leukemia (ALL). Our objective ranking of nuclear irregularity for 20 cases of ALL correlates well with the subjective ranking of two pathologists. Because our method scores irregularity on a population basis and independently of other morphological criteria, it is compatible for use with the French-American-British (FAB) classification system (1981) for ALL.

Cell Nucleus↗

Clinical uses of intravenous immunoglobulins.

PURPOSE: To ascertain the activity of intravenous immunoglobulin in a wide range of diseases. DATA IDENTIFICATION: English-language literature search using MEDLINE (1982 to 89), review of meeting reports, and extensive hand searching of bibliographies of identified articles. STUDY SELECTION: All identified articles. DATA EXTRACTION: Study quality and specific descriptive information concerning population, intervention, and outcome measurements were assessed. RESULTS OF DATA SYNTHESIS: There have been few controlled, randomized trials of intravenous immunoglobulin. Available data suggest efficacy in persons with primary immune deficiency, premature infants at risk for group B streptococcus infection, patients with Kawasaki disease, transplant recipients at risk for cytomegalovirus infection, patients with idiopathic thrombocytopenic purpura, and selected patients with chronic lymphocytic leukemia. Data are also favorable concerning the use of intravenous immunoglobulin in some other autoimmune disorders, but randomized trials are needed. Interesting areas for future study include the acquired immunodeficiency syndrome (AIDS), multiple myeloma, and lymphomas. Risks of intravenous immunoglobulin are minimal. CONCLUSION: Intravenous immunoglobulin is safe and effective in treating several human diseases. Additional randomized trials are needed.

Bacterial Infections↗

Relation of pooled logistic regression to time dependent Cox regression analysis: the Framingham Heart Study.

A standard analysis of the Framingham Heart Study data is a generalized person-years approach in which risk factors or covariates are measured every two years with a follow-up between these measurement times to observe the occurrence of events such as cardiovascular disease. Observations over multiple intervals are pooled into a single sample and a logistic regression is employed to relate the risk factors to the occurrence of the event. We show that this pooled logistic regression is close to the time dependent covariate Cox regression analysis. Numerical examples covering a variety of sample sizes and proportions of events display the closeness of this relationship in situations typical of the Framingham Study. A proof of the relationship and the necessary conditions are given in the Appendix.

Adult↗

Adult cardiac muscle cells in long-term serum-free culture: myofibrillar organization and expression of myosin heavy chain isoforms.

A culture system for adult rat cardiac muscle cells has been established without exposure of cells to serum at any step of the procedure. The methodology has been standardized and optimized to obtain better quality and high yield of cells and culture. Subsequent to enzyme perfusion, the release of myocytes from enzyme-perfused tissues was carried out in enzyme-free Joklik's medium instead of exposing cells to proteolytic enzyme(s) as done previously. Approximately 5 million cylindrical muscle cells per ventricle were obtained. The culture medium contained Eagle's minimum essential medium with Earle's salts, basic fibroblast growth factor, epidermal growth factor, insulin, transferrin, selenium, norepinephrine, triiodothyronine (T3), bovine serum albumin, nonessential amino acids, and ascorbic acid. The plating efficiency of the experimental cultures was comparable to that of the control cultures grown in the presence of serum. The cells in the serum-free medium contained myofibrillar and myosin isoforms characteristics of the adult myocytes. The cells underwent cellular reorganization comparable to that of the controls. The initial phase of reorganization involved the breakdown of myofibrils and extrusion of mitochondria, degraded myofibrils, and other cellular organelles. The latter phase of reorganization included myofibrillogenesis and organellogenesis resulting in the development of myofibrillar apparatus with cellular organelles. Myocytes were contractile throughout the culture period. Cardiac myocytes grown in serum-free medium expressed the predominant myosin isoform V1 similar to their counterparts in vivo. T3 is essential for the expression of isomyosin V1.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗