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Biomedical subjects

M Dang

Publications and source records attributed to M Dang.

13 recordsLinked to original sources
PubMed2001

Apoptosis in normal and neoplastic mammary gland development.

Apoptosis plays important roles in mammary development from early embryonic formation of the mammary gland to the regression that follows cessation of cycling. The most dramatic occurrence of apoptosis is found during mammary involution. Most of the secretory epithelium in the lactating breast undergoes apoptosis as the mammary gland regresses and is reorganized for another cycle of lactation. We used the morphology, biochemical changes, and gene expression detected in apoptotic mammary epithelium during involution as a model for studying cell death during other stages of mammary development and for approaching the failure of apoptosis found in mammary hyperplasia. Morphological studies and gene expression have suggested that apoptosis during involution is comprised of two phases: an early limited apoptosis in response to hormone ablation and later protease promoted widespread apoptosis in response to altered cell-matrix interactions and loss of anchorage. We examined protein expression during involution for changes associated with loss of hormone stimulation and altered cell-matrix interactions. One of the proteins whose expression is able to inhibit apoptosis, and is altered during mammary epithelial cell was the serine-threonine protein kinase, Akt 1. Akt 1 activation is common to hormone, growth factor, and anchorage-mediated survival of epithelial cells. We found regulated expression of activated Akt 1 in the mammary gland during involution. Akt 1 activation peaked in pregnancy and lactation, and decreased significantly during apoptosis in mammary involution. Mechanisms of Akt 1 action include modulation of the ratio bcl-2 family members implicated in control of apoptosis. Bcl-2 family proteins were also expressed in pattern consistent with Akt 1 regulation. These observations led us to examine expression of activated Akt 1 and bcl-2 family proteins in premalignant hyperplasias. Akt 1 activation was increased; expression of anti-apoptotic proteins bcl-2 and bcl-x was strongly increased while pro-apoptotic bax was greatly diminished in three different lines of transplantable premalignant mammary hyperplasia. This data suggest that activation of Akt 1 by hormone- or anchorage-mediated pathways regulates survival of mammary epithelium and can contribute to initiation of neoplasia. These data suggest that perturbation of normal cell turnover can contribute to initiation of neoplasia.

Animals↗
PubMed2000

Absence of amusia and preserved naming of musical instruments in an aphasic composer.

M.M., a right-handed, 74 year old professional musician and composer, presented with a progressive aphasia with a severe anomia. His musical competence was apparently totally preserved, and he continued his activity as a composer. There was a striking discrepancy between his impaired naming of nonmusical stimuli and his normal naming of musical instruments' sounds. We suggest that the preservation of skills in the musical domain results from an expanded cortical representation of this function in the left hemisphere, secondary to his lifelong formal training, and to the high level of his professional competence. As for his preserved naming of musical instruments, we argue that the early age-of-acquisition and higher than "normal" frequency/familiarity for names of musical instruments facilitate the access to their lexical representation and/or their retrieval within the lexicon.

Aged↗
PubMed2000

Modified Burow's wedge flap for upper lateral lip defects.

BACKGROUND: There are fundamental concepts we use in managing surgical defects. Whether planning a primary closure or a local flap, we frequently modify the basic design to maximize aesthetic outcomes, taking into consideration a number of factors including the location of the defect and tissue availability. OBJECTIVE: We describe a modified Burow's wedge flap for upper lateral lip defects. METHOD: Report of an illustrated case. RESULT: A patient with an upper lip defect was successfully reconstructed using the modified Burow's wedge flap, where the Burrow's wedge is placed on the mucocutaneous lip. CONCLUSION: Certain modifications of commonly used reconstructive techniques can be utilized in specific situations to enhance cosmesis. For the Burow's wedge flap, the dermatologic surgeon has several options in placing the Burow's triangle. This is an example of how alternatives in a closure can be used depending on the laxity of the skin and the size of the defect. Advantages and disadvantages of this alternative placement of the Burow's triangle are discussed.

Aged↗
PubMed2000

Stellate purse-string closure.

BACKGROUND: There are fundamental concepts we use in managing surgical defects. Whether planning a primary closure or a local flap, we frequently modify the basic design to maximize aesthetic outcomes, taking into consideration a number of factors including the location of the defect and tissue availability. OBJECTIVE: We describe the stellate modified purse-string closure, a novel flap modification. METHOD: Report of an illustrated case. RESULT: A patient with vertex scalp defect was reconstructed using the stellate purse-string flap. CONCLUSION: Certain modifications of commonly used reconstructive techniques can be utilized in specific situations to enhance cosmesis. Advantages of this modification are discussed.

Aged↗
PubMed1999

Rapid and efficient retrovirus-mediated gene transfer into B cell lines.

Murine B cell lines such as WEHI-231, BAL17 and M12.4.1 are frequently used as model systems to study signal transduction, cell cycle regulation, and apoptosis. Dissection of these processes often involves expressing exogenous genes in these cells. Electroporation is an inefficient method to express genes in B cell lines and requires several weeks to isolate and analyze clones, followed by an additional one to two weeks to grow sufficient cells for biochemical experiments (e.g. immunoprecipitations). In this report, we describe an optimized procedure for retroviral-mediated gene transfer into murine B cell lines that allows one to obtain a pure population of cells expressing an exogenous gene within 4 days. Two days post-infection, between 10% (BAL17 and M12.4.1 cells) and 70% (WEHI-231 cells) of the cells express the exogenous gene. Culturing the cells for an additional 48 hours with puromycin kills all the non-infected cells and yields a pure population of cells that express the exogenous gene. Sufficient cells for biochemical experiments can be obtained by expanding the cell culture for an additional 5 to 7 days. This rapid and efficient retroviral-mediated gene transfer procedure can greatly expedite the study of signal transduction and other processes in B cells.

Animals↗
PubMed1998

Comparison between enzyme-linked immunosorbent assay and cytotoxic cross-match procedures for detecting IgG anti-donor antibodies.

BACKGROUND: Disadvantages inherent to complement-dependent cytotoxicity cross-match (CDC XM) methods are the requirements for complement and viable target cells, detection of antibodies (Abs) against non-HLA antigens, and subjective scoring. Cross-Stat (SangStat Medical Corp., Menlo Park, CA), a recently developed enzyme-linked immunosorbent assay XM procedure for the detection of IgG anti-donor HLA Abs, is theoretically devoid of these flaws. METHODS: We compared results of Cross-Stat and our standard anti-human globulin (AHG)-enhanced CDC XM procedure on 524 sera from 230 transplant candidates, which were evaluated against 51 cadaveric donors. RESULTS: There was a significant correlation between AHG-CDC IgG XM and Cross-Stat results (P<0.001). For false negative sera, repeat AHG-CDC IgG XMs were still positive after platelet absorption, indicating that the Abs present were either non-HLA Abs or anti-HLA class II. Flow cytometry testing of false positive sera usually (42/62) substantiated Cross-Stat results, indicating that the discrepancy with AHG-CDC IgG XM is caused by greater sensitivity of Cross-Stat. Relative to the AHG-CDC XM, the sensitivity of Cross-Stat was 100%, the specificity was 93%, the positive predictive value was 73%, and the negative predictive value was 100%. A technical shortcoming of the Cross-Stat assay is that the frequency of indeterminate samples in the assays was 15%. Among 49 Cross-Stat negative vs. 13 Cross-Stat positive primary cadaveric renal allograft recipients (all AHG-CDC IgG-XM negative), there was no statistical difference in overall graft survival. CONCLUSION: Given the important theoretical advantages of enzyme-linked immunosorbent assay-based XM methods over the CDC XM, however, further testing of the clinical relevance of the Cross-Stat is warranted.

Enzyme-Linked Immunosorbent Assay↗
PubMed1998

Novel compound heterozygous mutations in the plectin gene in epidermolysis bullosa with muscular dystrophy and the use of protein truncation test for detection of premature termination codon mutations.

Absence of plectin, a large cytoskeleton-associated protein expressed in the skin and muscle, has been shown to underlie epidermolysis bullosa with muscular dystrophy (EB-MD), an autosomal recessive disorder (OMIM No. 226670). In the present study, we report the case of a patient who presented with neonatal blistering and late-onset muscular dystrophy with nail and tooth abnormalities, as well as severe mucocutaneous involvement including laryngeal webs and urethral strictures, features not previously reported in this syndrome. Mutation detection, based on the use of heteroduplex analysis, revealed that the proband was a compound heterozygote for two plectin mutations, 4416delC/4359ins13, both resulting in premature termination codons in the plectin rod domain. Because these mutations, and the majority of those previously reported, reside within exon 32 of the plectin gene (PLEC1), we applied the protein truncation test (PTT) to screen for mutations in the two large 3' exons (nos. 32 and 33) of PLEC1, which together comprise approximately 75% of the coding region of the gene. PTT readily detected truncated polypeptides in the proband profiled in this study, as well as in a patient in whom we have previously identified premature termination codon mutations in exon 32. Thus, PTT provides a rapid and reliable strategy to identify premature termination codon mutations from genomic DNA within PLEC1.

Adult↗
PubMed1995

Methotrexate therapy of psoriasis: differential sensitivity of proliferating lymphoid and epithelial cells to the cytotoxic and growth-inhibitory effects of methotrexate.

Although methotrexate (MTX) is one of the most clinically effective therapies employed to treat psoriasis, the mechanism by which low-dose MTX acts to modulate the hyperplasia of psoriasis, leading to the restoration of clinically normal skin, is only partially understood. MTX has been considered a cytotoxic agent that mediates its effect primarily on proliferating or cycling epidermal cells. Recently, proliferating lymphoid cells have been identified in psoriatic lesions, raising the possibility that proliferating lymphoid cells could be another target cell that is killed by MTX. In this study, we examined the growth-inhibitory and cytotoxic effects of MTX on proliferating lymphoid cells [THP-1 (macrophage), and MOLT-4 (T cell)], epithelial cells (HeLa, and HaCat), and normal human keratinocytes (NHK) in vitro. The proliferating cells were exposed to MTX for 24 h, and placed in fresh media to mimic the transient MTX blood levels that result from once-weekly therapy. THP-1 and MOLT-4 were found to be 10-100 times more sensitive to the cytotoxic effects of MTX than were HeLa and HaCat, and more than 1000 times more sensitive than primary human keratinocytes. At MTX concentrations that would be expected to occur in vivo during once-weekly therapy, a large percentage (> 95%) of proliferating lymphoid targets would be killed, and only a small percentage (< 10%) of proliferating epidermal cells would be affected. This in vitro data suggests that in psoriasis proliferating lymphoid cells are more likely than epithelial cells to be a major cellular target of MTX in vivo.

Cell Division↗
PubMed1994

Ultraviolet transmittance of contact lenses.

Chronic and acute exposure to ultraviolet (UV) radiation has been shown to have deleterious effects on all layers of the human eye. As a consequence, appropriate protective measures have been advocated with respect to exposure to this form of radiation. Among suggested actions are spending less time in the sun and wearing protective visual aids such as those containing UV-absorbing materials when exposed to sunlight. To investigate the protective ability of currently available contact lens materials we measured the transmittance characteristics of 11 different types of soft and rigid contact lenses in the UV and visible range from 280 to 500 nm with a Zeiss model DM4 Dual Beam Spectrophotometer. Our findings indicate that lenses not treated with UV absorbers transmitted most of the UV radiation. Lenses containing UV absorbers provided excellent UV protection and transmitted significantly less UV radiation than the untreated lenses (Student's t-test with Bonferoni's correction, N = 10, p < 0.001). Based on our findings, we recommend that contact lenses with UV absorbers be considered as a viable option for providing UV protection, especially for aphakic patients, patients taking photosensitizing pharmaceutical agents, and those patients who spend a great deal of time outdoors.

Absorption↗
PubMed1985

Determination of mouse liver 5-methyltetrahydrofolate concentration and polyglutamate forms.

The concentration and polyglutamate status of 5-methyltetrahydrofolate in mouse liver tissue extracts has been determined by enzymatic conversion to methylenetetrahydrofolate and subsequent entrapment of this cofactor form into a ternary complex with Lactobacillus casei thymidylate synthase and tritiated 5-fluorodeoxyuridylate. 5-Methyltetrahydrofolate was oxidized to methylenetetrahydrofolate using the reverse reaction of methylenetetrahydrofolate reductase with menadione as the ultimate electron acceptor. Reference 5-methyltetrahydrofolate could be quantitatively recovered from tissue extracts by this method. The polyglutamate status of enzymatically converted and complexed tissue 5-methyltetrahydrofolate was determined electrophoretically. Unlabeled 5-fluorodeoxyuridylate was used to remove endogenous methylenetetrahydrofolate prior to enzymatic oxidation of 5-methyltetrahydrofolate and subsequent electrophoretic analysis. In this manner, the 5-methyltetrahydrofolate polyglutamate pool alone could be labeled and visualized. There were no observable differences in the polyglutamate distribution of endogenous methylenetetrahydrofolate versus 5-methyltetrahydrofolate polyglutamates in extracts of normal mouse liver tissue.

Animals↗