Search PubMed⌕ Search

Biomedical subjects

M L Lee

Publications and source records attributed to M L Lee.

At least 127 records · Page 7Linked to original sources
PubMed1994

Endothelial cell adhesion molecules in psoriasis.

Skin biopsies from patients with psoriasis and normal controls were examined for the expression of cell adhesion molecules including intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1), HECA-452 and 4D10, using an immunoperoxidase techique. This study demonstrates that psoriatic skin exhibits a wide variety of markers of endothelial cell activation which are either induced or increased in expression (ICAM-1, ELAM-1 & 4D10). Moreover, ICAM-1 & HECA-452 are also expressed on leukocytes. These antigens may facilitate the adhesion of inflammatory cells to endothelium and antigen-presenting cells in psoriatic skin. Thus, they may play a role in faciliating the infiltration of leukocytes into psoriatic skin.

Adult↗
PubMed1994

Mixed-effect models for predicting microbial interactions in the vaginal ecosystem.

Three statistical models that predict microbial interactions within the vaginal environment are presented. A large data set was assembled from in vivo studies describing the healthy vaginal environment, and the data set was analyzed to determine whether statistical models which would accurately predict the interactions of the microflora in this environment could be formulated. During assembly of the data set, two new variables were defined and were added to the data set, that is, cycle (sequence of menstrual cycle) and flow stage (subdivision of cycle determined by day of menstrual cycle). Concentrations of total aerobic (includes facultative) bacteria, total anaerobic bacteria, and a Corynebacterium sp. were identified by correlation analysis as variables with significant predictors. By using a regression method with a backward elimination procedure, significant predictors of these outcome variables were identified as the concentrations of Lactobacillus spp., anaerobic Streptococcus spp., and Staphylococcus spp., respectively. For all three outcome variables, pH and flow stage were also identified as significant independent variables. Because some of the data in the data set are repeated measurements for a subject, a mixed-effect model that accounts for the random effects of repeated-measurement data fit best the data set for predicting interactions between various members of the vaginal microflora. The predictive accuracies of the three models were tested by a comparison of model-predicted outcome-variable values with actual mean in vivo outcome-variable values. From these results, we concluded that it is possible to accurately predict vaginal microflora interactions by using a mixed-effect modeling system. The application of this type of modeling strategy and its future use are discussed.

Colony Count, Microbial↗
PubMed1994

Antitumor activity of a piperidine phospholipid.

A piperidine phospholipid ((+/-)-2-[hydroxy] [1-octadecyloxycarbonylpiperidin-3-yl]methoxy-phosphinyl] oxy]-N,N,N, trimethylethaniminium hydroxide inner salt, SDZ 62-826) has been prepared that exhibited weak direct cytotoxicity and strong macrophage-induced cytotoxicity in vitro against a variety of murine and one human tumor cell lines. This compound was found to be as effective as ET-18-OCH3 and SRI 62-834, phospholipids with both strong direct and macrophage-induced cytotoxicity, in increasing survivors and reducing tumor volume when given either orally or intravenously in the mouse MethA fibrosarcoma model. These findings suggest that the macrophage-induced cytotoxicity exhibited by ET-18-OCH3 and other phospholipids may play an important role in this tumor model.

Animals↗
PubMed1993

Solute adsorption on polymer-coated fused-silica capillary electrophoresis columns using selected protein and peptide standards.

Three series of basic proteins and peptides were selected for use in studying the adsorption behavior of fused-silica capillary electrophoresis columns. A comparative study of untreated and treated fused-silica columns was done. The polymers used as coating materials ranged from very hydrophobic to very hydrophilic. The average efficiency of weakly hydrophilic Ucon-coated capillaries for basic proteins was over 1 million theoretical plates at a buffer pH of 4.8. For this coating, it was found that the maximum column efficiency was obtained at a film thickness of approximately 100 nm. It was easily seen that both ionic and hydrophobic interaction forces can play important roles in protein adsorption onto the capillary walls. Furthermore, strongly hydrophilic polymer coatings may possibly lead to hydrogen-bonding interactions, which decrease column efficiency. Studies have been conducted using two series of polypeptides with varying chain lengths. One series was used to study the effect of polypeptide chain length on retention behavior. Efficient separations of bioactive peptide drugs on Ucon-coated columns were achieved. The results indicate that high efficiency and resolution of basic peptides tested can be realized on columns modified with weakly hydrophilic polymers at a pH value of about 5.

Adsorption↗
PubMed1993

Effects of administration of an anti-CD5 plus immunoconjugate in rheumatoid arthritis. Results of two phase II studies. The CD5 Plus Rheumatoid Arthritis Investigators Group.

OBJECTIVE: To evaluate the safety and activity of an immunoconjugate of ricin A chain and anti-CD5 monoclonal antibody (anti-CD5 IC), with and without concomitant methotrexate and/or azathioprine, in the treatment of rheumatoid arthritis (RA). METHODS: Seventy-nine patients with active RA were enrolled in 2 prospective open-label protocols. RESULTS: Using composite criteria, response rates were 50-68% at 1 month and 22-25% at 6 months. Transient depletion of CD3/CD5 T cells was observed on days 2 and 5 of treatment, with reconstitution on day 15 or day 29. Treatment-associated adverse effects were common but resolved rapidly without sequelae. CONCLUSION: These findings suggest activity of anti-CD5 IC in active RA and warrant confirmation in a multicenter randomized study (currently underway).

Adult↗
PubMed1993

Association of protein kinase C activation with induction of ornithine decarboxylase in murine but not human keratinocyte cultures.

The goal of this study was to compare the response of mouse epidermal keratinocytes (MEKs) and human epidermal keratinocytes (HEKs) to 12-O-tetradecanoylphorbol-13-acetate (TPA) with respect to the activation and downregulation of protein kinase C (PKC), the expression of c-jun and c-fos, and the expression and induction of ornithine decarboxylase (ODC) activity. Keratinocytes from adult CD-1 mice and from discarded adult human skin were grown in primary culture in a high-calcium serum-free medium that supported proliferation and differentiation. Immunoblotting of freshly isolated and cultured MEKs and HEKs for isozymes of protein kinase C revealed that fresh HEKs contained PKC alpha, PKC beta, and PKC delta; no PKC gamma, PKC epsilon, or PKC zeta were detected. In fresh MEKs, PKC alpha, PKC beta, PKC delta, and PKC zeta were observed, but not PKC gamma or PKC epsilon. After 2 wk in culture, the isozyme profiles of MEKs and HEKs were similar except that PKC gamma was noticeably present in HEK cultures. Activation of partially purified total PKC by TPA was similar in freshly isolated and cultured MEKs and HEKs, indicating that the two species were similar in this regard and that 2 wk of culture did not alter this characteristic. When MEK and HEK cultures were treated with TPA for 3 h, less than 30% of the control level of PKC activity was detected, indicating that TPA-induced downregulation of PKC was similar in MEKs and HEKs. After treatment with TPA, MEK cultures produced a large induction of both c-jun and c-fos mRNA by 60 min, as determined by northern blot analysis, and a large induction of ODC mRNA and enzyme activity by 6 h. TPA treatment of cultured HEKs, however, did not induce ODC activity; in fact, less activity, compared with that of control cultures, was observed. Northern blot analysis also revealed no increase in c-jun, c-fos, and ODC mRNA in HEKs. However, c-jun and c-fos mRNA and both ODC mRNA and enzyme activity were induced in HEKs fed growth factors after several days of deprivation. This suggests that the lack of ODC induction by TPA in HEKs is probably due to species differences in downstream steps in PKC signal transduction.

Adult↗
PubMed1993

Augmented lymphocyte binding to cultured endothelium in psoriasis.

Lymphocyte binding to cultured human umbilical vein endothelial cells was evaluated using a modified centrifugation binding assay in 15 patients with psoriasis and compared with three patients with atopic dermatitis, 11 patients with rheumatoid arthritis and 28 normal controls. Patients with psoriasis demonstrated 61% augmented lymphocyte binding compared with normal controls (P < 0.0001), which was not explained by differences in age and sex or an effect of psoriatic sera. In serial studies of six patients, this difference was found to be reversible with treatment and clinical improvement. Lymphocytes from patients with atopic dermatitis demonstrated decreased binding to endothelium (P < 0.005), while those from patients with rheumatoid arthritis were not different from normal controls. This is the first skin disease described in which augmented lymphocyte binding to endothelium occurs, and may represent a mechanism by which lymphocytes are targeted to psoriatic skin.

Adolescent↗
PubMed1992

Differential effects of dietary linoleic acid on mouse skin-tumor promotion and mammary carcinogenesis.

On the basis of reports of rat mammary- and pancreas-tumor models, we hypothesized that an increase in consumption of linoleic acid (LA) would also cause an enhancement in mouse skin-tumor promotion. SEN-CAR mice were placed on diets containing 0.8%, 2.2%, 3.5%, 4.5%, 5.6%, 7.0%, or 8.4% LA, 1 week after initiation with 7,12-dimethylbenz(a)anthracene and 3 weeks before starting promotion with 12-O-tetradecanoylphorbol-13-acetate. An inverse correlation (r = -0.92) was observed between papilloma number and level of LA; however, there was little difference in tumor incidence. A relationship between diet and carcinoma incidence was also found. The fatty acid composition of epidermal phospholipids reflected the dietary LA levels. 12-O-Tetradecanoylphorbol-13-acetate-induced epidermal prostaglandin E2 levels generally decreased with increasing dietary LA. To determine whether this inverse correlation between dietary LA and tumor yield was due to species differences or organ-model differences, a mammary carcinogenesis experiment was performed. SENCAR mice were fed the 0.8%, 4.5%, and 8.4% LA diets. All mice received 6 mg 7,12-dimethylbenz(a)anthracene, administered intragastrically at 1 mg/week. Tumor appearance was delayed in the 0.8% LA diet group, and a positive dose-response relationship between dietary LA and mammary-tumor incidence was observed. These studies suggest that the effect of dietary LA on tumor development is target tissue specific rather than species specific.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Low level mosaicism for a balanced 7;14 translocation in the father of an abnormal 7q+ child.

A child with a 7q+ chromosome abnormality had a father with 0.5% mosaicism for a balanced 7;14 translocation. This mosaicism was not found in 100 fibroblasts. This degree of mosaicism is well below the limits usually detected by standard clinical cytogenetic protocols. However, the one abnormal cell cannot be disregarded in this case, since it can serve as an explanation of the child's genotype. This case serves to illustrate the need for detecting subtle degrees of mosaicism for structural anomalies in humans and brings to question the true population frequencies of mosaic balanced translocation carriers.

Chromosome Aberrations↗
PubMed1992

The effect of dietary fat on the rapid development of mammary tumors induced by 7,12-dimethylbenz(a)anthracene in SENCAR mice.

We recently reported (J. Leyton et al., Cancer Res., 51: 907-915, 1991) an inverse correlation between skin tumor number and level of dietary linoleic acid (LA) in SENCAR mice following an initiation-promotion protocol. These results differed from the reported (C. Ip et al., Cancer Res., 45: 1997-2001, 1985) positive correlation between dietary LA and tumor incidence for the rat mammary gland. The goal of the study reported here was to determine whether this dissimilarity was due to organ site or species differences. Female SENCAR mice were fed 1 of 3 15% fat diets containing LA at levels of 0.8, 4.5, and 8.4% before, during, and after intragastric administration of 6 mg (1 mg/week) 7,12-dimethylbenz(a)anthracene. A positive correlation between level of dietary LA and mammary tumor incidence was observed such that for the first 15 weeks, the incidence was greatest in the 8.4% LA diet group, followed by the 4.5% and then the 0.8% LA groups. Distinct dietary effects on latency were also noted in that 15, 12, and 8 weeks after cessation of 7,12-dimethylbenz(a)anthracene were required for a 40% carcinoma incidence in the 0.8, 4.5, and 8.4% LA diet groups, respectively. A histopathological analysis of all tumors revealed that the predominant type was the adenosquamous carcinoma, which comprised 46.6, 54.1, and 77.7% of all mammary tumors for diets containing 0.8, 4.5, and 8.4% LA, respectively. The second most common tumor was the adenocarcinoma type B, which was found with a frequency of 33% in the 0.8% and 4.5% LA diet groups and 22% in the 8.4% LA diet group. These results indicate that SENCAR mice have a short latency period for 7,12-dimethylbenz(a)anthracene-induced mammary tumor development and that rat and mouse mammary tumor development is modified by dietary LA in a similar manner, although in the SENCAR mouse dietary LA did not have a saturating effect. In addition, high dietary LA was found to be associated specifically with an increased incidence of adenosquamous carcinomas but not of other types of mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Treatment of hemophilia A with a highly purified factor VIII concentrate prepared by anti-FVIIIc immunoaffinity chromatography.

To reduce the risk of pathogenic virus transmission associated with the therapeutic administration of plasma-derived anti-hemophilic factor (FVIIIc), a process utilizing anti-FVIIIc immunoaffinity chromatography to isolate FVIIIc has been developed. In addition, the starting cryoprecipitate solution has been treated with an organic solvent/detergent mixture to inactivate lipid-enveloped viruses. A final ion exchange chromatography step is used to further remove contaminants, e.g., anti-FVIIIc antibody, potentially leached with FVIIIc during the immunoaffinity step. The purified FVIII is stabilized for lyophilization and storage by the addition of human albumin. The monoclonal anti-FVIIIc antibody used in the immunoaffinity step of the process is not detectable in the final preparation. Viral reduction studies performed at specific steps of the process demonstrate that 11 logs of human immunodeficiency virus (HIV) and greater than 4-5 logs of other lipid-enveloped viruses are inactivated within the first 30 s of exposure to the solvent/detergent mixture and 4-5 logs of various model viruses, e.g. Endomyocarditis virus (EMC), are physically removed during washing of the immunoaffinity column. The lyophilized product is reconstituted using sterile water in a matter of seconds. The pharmacokinetics of Hemofil M were compared to those obtained using a standard heat-treated concentrate (Hemofil CT) in five severe factor VIII deficient hemophiliacs in a randomized, cross-over study. No statistically significant differences were observed in mean half life (p greater than 0.6) or median recovery (p = 0.4) between the two preparations. No clinically significant adverse effects were observed in patients receiving either FVIII preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1992

TPA has no influence on the expression of myosin heavy chain isoforms in cultured adult cardiac muscle cells.

The effect of a tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), on the expression of myosin heavy chain isoforms in cultured rat cardiac ventricular muscle cells was studied. The previous preliminary report [Claycomb WC (1988): "Biology of Isolated Adult Cardiac Myocytes." In Clark WA, Decker RS, Borg TK (eds): New York: Elsevier, pp 284-287] indicated that TPA turns off the expression of myosin heavy chain genes in cultured adult cardiac myocytes. Electrophoretic and immunocytochemical analyses were carried out in the present studies. The myosin heavy chain isoform profiles of cardiac myocytes exposed to TPA at concentrations of 50-250 ng/ml culture medium for varying periods were similar to those of controls that were grown in the absence of TPA, showing predominant isoform V1. Immunofluorescence microscopy with monoclonal antibodies to cardiac ventricular isomyosin revealed the structural organization of myosin in TPA-treated cells. The organization of myosin was variable among different myocytes and within a single myocyte. Immunofluorescence microscopy was extended to the examination of the organization of alpha-actinin which did not differ from that of myosin in some myocytes. In contrast to the previous report [Claycomb, 1988], this study has demonstrated that TPA has no influence on the expression of myosin heavy chain isoforms in cultured adult ventricular cardiac muscle cells.

Actinin↗
PubMed1992

Trisomy 5 mosaicism detected prenatally with an affected liveborn.

This paper reports a case of chromosomal mosaicism for trisomy 5 recovered from amniotic fluid cells and from skin fibroblasts of a liveborn dysmorphic male. Routine amniocentesis was performed at 16 weeks' gestation because of parental concern. Trisomy 5 cells were measured from 25 per cent of amniocytes from two culture vessels. No further invasive testing was performed until 32 weeks' gestation, at which time ultrasound examination showed a fetus with intrauterine growth retardation. Fetal blood sampling was then performed, with only karyotypically normal cells recovered. At birth, the child was found to have multiple dysmorphic features and congenital anomalies, including an eventration of the diaphragm and ventricular septal defect, both of which required surgical correction. Chromosomal analysis of cord blood lymphocytes indicated 46,XY; however, 20 per cent of the cultured fibroblasts obtained from the chest skin at the incision site for diaphragmatic repair had a 47,XY, +5 karyotype. Trisomy 5 mosaicism may be another example of tissue-limited mosaicism. Fetal blood sampling can then be falsely reassuring. Furthermore, because some cell lines rarely appear in lymphocyte populations, cytogenetic analysis of multiple tissues is warranted as part of the evaluation of individuals with developmental delay and dysmorphic features.

Abnormalities, Multiple↗
PubMed1992

High resolution separation and quantitation of ribonucleotides using capillary electrophoresis.

A method for the analysis of ribonucleotides using capillary electrophoresis has been developed. A cross-linked polyacrylamide coated column, Tris-HCl, and phosphate-mixed buffer were used, which produced reproducible separations (solute migration time average RSD% of 1.2) of 14 ribonucleotides within 50 min. Linear relationships between peak areas and sample concentrations, an average minimum detectable concentration of 5.4 microM, and an average minimum detectable quantity of 0.08 pmol were obtained. The described method allowed reproducible and reliable qualitative and quantitative analysis of intracellular ribonucleotide pools in HeLa cells.

Capillary Action↗
PubMed1992

Risk of malignancy in bilateral streak gonads: the role of the Y chromosome.

Although girls with Turner's syndrome (45,X) are not at risk for malignancy, patients with feminizing testicular syndrome with XY chromosome composition and patients with "mixed gonadal dysgenesis" are at risk for malignancy, and bilateral gonadectomy is performed. We have treated seven girls with "Turner-like" syndrome, who we believe are also "at risk" for development of malignancy and in whom gonadectomy should be performed. We present seven cases of phenotypically typical females, without sexual ambiguity, who presented with primary amenorrhea and short stature (5) and/or minor dysmorphic features (2). Chromosome analysis showed 45,X karyotype plus a fragment that we could not rule out as being part of a Y chromosome (in one patient a complete Y chromosome). In two patients, the fragment was subsequently positively identified as a Y, using a DNA probe. In view of the known high incidence of development of gonadoblastoma in the dysgenetic gonads of phenotypic females with a Y chromosome, bilateral gonadectomy was performed in these girls. Bilateral genital streaks with normal uterus and Fallopian tubes were found in all patients. In two patients unsuspected gonadoblastoma, without metastases, was found. In five cases, Leydig cells and tubular structures resembling rete testes were found, cells that are associated with Y-chromosomal tissue. We stress the need for complete chromosomal evaluation of phenotypically female patients with primary amenorrhea or features of Turner's syndrome. If a Y chromosome or the possibility of a Y chromosome cannot be excluded, gonadectomy should be performed because of the risk of malignancy.

Adolescent↗