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Biomedical subjects

M Hwang

Publications and source records attributed to M Hwang.

At least 19 recordsLinked to original sources
PubMed2006

Systemic herpes simplex virus infection following cadaveric renal transplantation: a case report.

Herpes simplex virus (HSV) infection usually occurs in immunocompromised or severely debilitated patients. It is not so common in patients with renal transplants. The diagnosis can only be made histologically. It usually occurs during or shortly after treatment of graft rejection with high-dose steroids. We have recently experienced a case of HSV esophagitis and nephropathy in the renal allograft biopsy, which was identified by histology, immunostaining, and electron microscopy. A 43-year-old woman underwent cadaveric renal transplantation with cyclosporine and prednisolone treatment. Twelve months later, she developed renal insufficiency and proteinuria. Allograft renal biopsy showed some evidence of acute rejection. She was treated with 3 successive days of methylprednisolone (1.0 g/d) intravenously and continued tapering of steroids. Three weeks after steroid pulse therapy, she had throat pain, oral cavity ulcer, dysphagia, and febrile sensation. Esophagoscopy revealed multiple confluent ulcers in the whole esophagus, and biopsy showed enlarged epithelial cells with prominent nuclei. Immunohistochemically, the epithelial cells were positive with a monoclonal antibody to HSV type 1. She was started on acyclovir intravenously, which was continued for a week. After a week, her symptoms began to improve and repeat endoscopy showed no residual esophagitis. A renal allograft infection with HSV can persist in heavily immunosuppressed patients with recurrent rejection episodes. HSV mainly affects tubular cells causing necrosis, a major reason for functional deterioration. A biopsy is required for diagnosis.

Acyclovir↗
PubMed2005

The homeodomain transcription factor Pitx3 facilitates differentiation of mouse embryonic stem cells into AHD2-expressing dopaminergic neurons.

The A9 dopaminergic (DA) neuronal group projecting to the dorsal striatum is the most vulnerable in Parkinson's disease (PD). We genetically engineered mouse embryonic stem (ES) cells to express the transcription factors Nurr1 or Pitx3. After in vitro differentiation of Pitx3-expressing ES cells, the proportion of DA neurons expressing aldehyde dehydrogenase 2 (AHD2) increased, while the total number of DA neurons remained the same. The highest levels of AHD2 expression were observed in mouse A9 DA neurons projecting to the dorsal striatum. Furthermore, real-time PCR analyses of in vitro differentiated Pitx3-expressing ES cells revealed that genes highly expressed in A9 DA neurons were up-regulated. When transplanted into the mouse striatum, Pitx3-expressing cells generated an increased proportion of AHD2-expressing DA neurons. Contrastingly, in Nurr1-expressing ES cells, increases of all midbrain DA markers were observed, resulting in a higher total number of DA neurons in vitro and in vivo, whereas the proportion of AHD2-expressing DA neurons was not changed. Our data, using gain-of-function analysis of ES cells, suggest that Pitx3 may be important for specification and/or maintenance of A9-like neuronal properties, while Nurr1 influences overall midbrain DA specification. These findings may be important for modifying ES cells to generate an optimal cell source for transplantation therapy of PD.

Alcohol Dehydrogenase↗
PubMed2005

The temporal and spatial expression of the novel Ca++-binding proteins, Scarf and Scarf2, during development and epidermal differentiation.

During the process of epidermal differentiation, intracellular and extracellular calcium (Ca++) concentrations induce an array of signaling pathways . Keratinocytes follow a complex Ca++-dependent program of differentiation moving from the basal proliferative layer, through the spinous and granular differentiated layers to ultimately culminate in the formation of the cornified layer of the epidermis. Members of the Ca++-binding proteins play a central role in the transduction of Ca++ signals. Utilizing a suppressive subtractive hybridization screen comparing basal and differentiated keratinocytes, we identified the novel Ca++-binding protein genes, Scarf (skin Calmodulin-related factor) and Scarf2, which have homology to calmodulin (CaM). In this study, we present a comprehensive analysis of the expression pattern for Scarf and Scarf2 transcripts and proteins in the developing mouse. To examine Scarf2 expression during embryogenesis, we performed in situ hybridization, and detected expression in the hair follicle, skin and nasal epithelium. These results showed substantial overlap with the previously reported Scarf gene expression [Hwang, M., Morasso, M.I., 2003. The novel murine Ca2+-binding protein, Scarf, is differentially expressed during epidermal differentiation. J. Biol. Chem. 278, 47827-47833]. Comparing the expression patterns of Scarf and Scarf2 proteins in neonatal and adult mouse skin with several structural epidermal proteins, i.e. keratin 14 (K14), keratin 1 (K1), loricrin (LOR) and filaggrin (FIL) showed that their expression overlaps K1, an early marker of keratinocyte differentiation. Interestingly, Scarf and Scarf2 were also detected in the tongue and oral epithelia, rib bone undergoing ossification and in the medullar region of thymus.

Amino Acid Sequence↗
PubMed2000

Pure trigeminal motor neuropathy: a case report.

Pure trigeminal motor neuropathy is a trigeminal motor paralysis unaccompanied by signs of trigeminal sensory or other cranial nerve involvement. We present a case of a 38-year-old man complaining of progressive weakness and wasting of the right masticatory muscles after a bout of mild cold symptoms. No sensory symptoms were present. History, neurologic examination, electrophysiologic studies, and magnetic resonance imaging of the brain led to the diagnosis of pure trigeminal motor neuropathy. The cause may have been an autoimmune reaction to a viral infection.

Adult↗
PubMed1999

New mutations, polymorphisms, and rare variants in the ATM gene detected by a novel SSCP strategy.

The gene for ataxia-telangiectasia, ATM, spans about 150 kb of genomic DNA. ATM mutations are found along the entire gene, with no evidence of a mutational hot spot. Using DNA as the starting material, we screened the ATM gene in 92 A-T patients, using an optimized single-strand conformation polymorphism (SSCP) technique that detected all previously known mutations in the polymerase chain reaction (PCR) segments being analyzed. To expedite screening, we sequentially loaded the SSCP gels with three different sets of PCR products that were pretested to avoid overlapping patterns. Many of the DNA changes we detected were intragenic polymorphisms. Of an expected 177 unknown mutations, we detected approximately 70%, mostly protein truncating mutations (that would have been detectable by protein truncation testing if RNA starting material had been available). Mutations have now been defined for every exon of the ATM gene. Herein, we present 35 new mutations and 34 new intragenic polymorphisms or rare variants within the ATM gene. This is the most comprehensive compilation of ATM polymorphisms assembled to date. Defining polymorphic sites as well as mutations in the ATM gene will be of great importance in designing automated methods for detecting mutations.

Ataxia Telangiectasia↗
PubMed1999

Derivational suffix productivity for students with and without language-learning disabilities.

The effect of productivity (a correlate of suffix frequency) on students' derivational suffix use was investigated with students with and without language-learning disabilities (LLD). Sixty-nine elementary- to middle-school-age students participated in an elicitation task (in which they produced derived forms) and a forced-choice task (in which they selected derived forms) to label nonsense objects and events. In each task, students used highly productive suffixes to convey a given meaning. For example, students used the highly productive suffix er rather than the less productive suffix ant to convey an agentive meaning and used the more productive suffix let instead of the unproductive suffix kin to convey a diminutive meaning. Also, productivity appeared to guide accuracy of suffix use across meanings. For example, the agentive suffix er was produced with much higher accuracy than the less productive diminutive suffix let. In general, patterns of performance within and across meanings were the same for students with and without LLD. LLD students were less accurate in determining the meanings conveyed by derivational suffixes than typically achieving students matched for chronological age. However, their performance was similar to typically achieving students with comparable language skills.

Child↗
PubMed1999

Children's auditory lexical decisions: a limited processing capacity account of language impairment.

Twenty-three school-age children with language impairments (LI) and 46 typically achieving children participated in 2 auditory lexical decision tasks. Effects of phonological opacity (i.e., stress and vowel changes involved in forming derivatives from a base word) on word recognition were investigated. In one task, children made lexical decisions about phonologically transparent real derivatives (e.g., hatless) and pseudo derivatives (e.g., *quickless). In this task, children with LI showed only subtle deficits compared to their chronological-age (CA) peers. In the other task, children made lexical decisions about phonologically opaque real derivatives (e.g., acidity) and pseudo derivatives (e.g., *combinity) as well as transparent derivatives. In this task, children with LI were substantially less accurate than were CA children in identifying phonologically opaque real derivatives and were slower to do so than both CA and language-age (LA) children. Children in the LI and LA groups were slower than children in the CA group to identify phonologically opaque pseudo derivatives. These results are interpreted within a limited processing capacity account of language impairment.

Child↗
PubMed1999

Testing the generalized slowing hypothesis in specific language impairment.

This study investigated the proposition that children with specific language impairment (SLI) show a generalized slowing of response time (RT) across tasks compared to chronological-age (CA) peers. Three different theoretical models consistent with the hypothesis of generalized slowing--a proportional, linear, and nonlinear model--were examined using regression analyses of group RT data. Each model was an excellent fit with the RT data. The most parsimonious model indicated that the SLI group was proportionally slower than the CA group. Mean RTs of the SLI group were about one fifth slower across tasks than the CA group's mean RTs. Less slowing was evident for a subgroup of young children with expressive SLI than for children with mixed (expressive and receptive) SLI. Although the mean RT data reflected many individual SLI children's RT performance, not all SLI children showed generalized slowing.

Age Factors↗
PubMed1996

Effect of combination of suboptimal concentrations of P-glycoprotein blockers on the proliferation of MDR1 gene expressing cells.

Pharmacologically active in vivo doses of P-glycoprotein (Pgp) blockers, specifically verapamil, Cremophor EL and PSC833 cause toxicity in addition to that from the concomitantly used cancer chemotherapeutic drugs. It was shown before that these blockers cause different types of toxicities in vivo. We found that these 3 chemically distinct Pgp blockers exert different biophysical effects on the membranes of L1210 MDR cells. They also affect the general metabolism of these cells differently, but all block affinity labeling of Pgp. We could also show that the combination of suboptimal doses of these blockers can restore the uptake of the Pgp substrate rhodamine 123 into L1210MDR, 3T3MDR and KB-VI cells and can reduce the survival rate of these cells when treated in combination with daunorubicin. Our results suggest that the combination of suboptimal doses of these Pgp blockers may be advantageous in clinical practice.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs.

ERCC4 is an essential human gene in the nucleotide excision repair (NER) pathway, which is responsible for removing UV-C photoproducts and bulky adducts from DNA. Among the NER genes, ERCC4 and ERCC1 are also uniquely involved in removing DNA interstrand cross-linking damage. The ERCC1-ERCC4 heterodimer, like the homologous Rad10-Rad1 complex, was recently found to possess an endonucleolytic activity that incises on the 5' side of damage. The ERCC4 gene, assigned to chromosome 16p13.1-p13.2, was previously isolated by using a chromosome 16 cosmid library. It corrects the defect in Chinese hamster ovary (CHO) mutants of NER complementation group 4 and is implicated in complementation group F of the human disorder xeroderma pigmentosum. We describe the ERCC4 gene structure and functional cDNA sequence encoding a 916-amino-acid protein (104 kDa), which has substantial homology with the eukaryotic DNA repair and recombination proteins MEI-9 (Drosophila melanogaster), Rad16 (Schizosaccharomyces pombe), and Rad1 (Saccharomyces cerevisiae). ERCC4 cDNA efficiently corrected mutants in rodent NER complementation groups 4 and 11, showing the equivalence of these groups, and ERCC4 protein levels were reduced in mutants of both groups. In cells of an XP-F patient, the ERCC4 protein level was reduced to less than 5%, consistent with XPF being the ERCC4 gene. The considerable identity (40%) between ERCC4 and MEI-9 suggests a possible involvement of ERCC4 in meiosis. In baboon tissues, ERCC4 was expressed weakly and was not significantly higher in testis than in nonmeiotic tissues.

Amino Acid Sequence↗
PubMed1995

Induction of depersonalization by the serotonin agonist meta-chlorophenylpiperazine.

Sixty-seven subjects, including normal volunteers and patients with obsessive-compulsive disorder, social phobia, and borderline personality disorder, received ratings of depersonalization after double-blind, placebo-controlled challenges with the partial serotonin agonist meta-chlorophenylpiperazine (m-CPP). Challenge with m-CPP induced depersonalization significantly more than did placebo. Subjects who became depersonalized did not differ in age, sex, or diagnosis from those who did not experience depersonalization. There was a significant correlation between the induction of depersonalization and increase in panic, but not nervousness, anxiety, sadness, depression, or drowsiness. This report suggests that serotonergic dysregulation may in part underlie depersonalization.

Adult↗
PubMed1995

Correction of chromosomal instability and sensitivity to diverse mutagens by a cloned cDNA of the XRCC3 DNA repair gene.

The mutagen-sensitive CHO line irs1SF was previously isolated on the basis of hypersensitivity to ionizing radiation and was found to be chromosomally unstable as well as cross-sensitive to diverse kinds of DNA-damaging agents. The analysis of somatic cell hybrids formed between irs1SF and human lymphocytes implicated a human gene (defined as XRCC3; x-ray repair cross-complementing), which partially restored mitomycin C resistance to the mutant. A functional cDNA that confers mitomycin C resistance was transferred to irs1SF cells by transforming them with an expression cDNA library and obtaining primary and secondary transformants. Functional cDNA clones were recovered from a cosmid library prepared from a secondary transformant. Transformants also showed partial correction of sensitivity to cisplatin and gamma-rays, efficient correction of chromosomal instability, and substantially improved plating efficiency and growth rate. The XRCC3 cDNA insert is approximately 2.5 kb and detects an approximately 3.0-kb mRNA on Northern blots. The cDNA was mapped by fluorescence in situ hybridization to human chromosome 14q32.3, which was consistent with the chromosome concordance data of two independent hybrid clone panels.

Animals↗
PubMed1995

Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S).

The alpha-L-iduronidase deficiency diseases (Mucopolysaccharidosis I) cover a spectrum of clinical severity ranging from the very severe (Hurler syndrome, MPS IH) through an intermediate (Hurler/Scheie syndrome, MPS IH/S) to a relatively mild form (Scheie syndrome, MPS IS). Numerous mutations of the gene encoding alpha-L-iduronidase (IDUA) are known in Hurler syndrome, but only three in the other disorders. We report on novel mutations of the IDUA gene in one patient with the Scheie syndrome and in three patients with the Hurler/Scheie syndrome. The novel mutations, all single base changes, encoded the substitutions R492P (Scheie), and X654G, P496L, and L490P (Hurler/Scheie). The L490P mutation was apparently homozygous, whereas each of the others was found in compound heterozygosity with a Hurler mutation. The deleterious nature of the mutations was confirmed by absence of enzyme activity upon transfection of the corresponding mutagenized cDNAs into Cos-1 cells. These results provide additional information for genotype-phenotype correlations.

Adult↗
PubMed1995

Assessment of outcome of bifurcation lesions and non-bifurcation lesions treated in the CAVEAT trial. CAVEAT investigator group.

Registry data suggests that bifurcation lesions are associated with reduced success during percutaneous revascularization. We studied 1012 CAVEAT patients to compare procedural outcomes in patients with and without bifurcation lesions whose target vessel was treated with either atherectomy or angioplasty. Bifurcation lesions have increased angiographic complexity and interventions on them are associated with lower acute procedural success rates compared to non-bifurcation lesions. Subgroup analysis suggests that atherectomy treatment of bifurcation lesions improves acute procedural success rates and lowers restenosis rates compared to angioplasty treatment of bifurcation lesions but atherectomy of bifurcation lesions is associated with higher acute complication rates than angioplasty of bifurcation lesions.

Adult↗
PubMed1994

Acute procedural results in the treatment of 30 coronary artery bifurcation lesions with a double-wire atherectomy technique for side-branch protection.

Percutaneous treatment of bifurcation lesions has been consistently shown to be associated with lower acute success rates, higher initial complication rates, and an increased rate of restenosis when compared with findings in nonbifurcation lesions. Recent analysis of data from a CAVEAT subgroup suggests that directional atherectomy of bifurcation lesions can improve initial success rates and lower restenosis rates but at the cost of high complication rates. Reports from several angioplasty series document improved success rates and lower complication rates with the use of a two-wire technique to protect side branches when treating bifurcation lesions. Our experience with a two-wire atherectomy technique that uses a nitinol wire to protect important side branches is presented.

Adult↗
PubMed1993

Immunoaffinity purification of dietary heterocyclic amine carcinogens.

Cooking meats produces a family of heterocylic aromatic amines that are carcinogens in rodents and genotoxic in many short-term assays. Concern that these compounds may be human carcinogens has prompted us to develop immunochemical methods for quantifying these compounds in the human diet and for identifying the parent compounds and metabolites in urine and feces. Previously reported monoclonal antibodies to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 6-phenyl-2-amino-1-methylimidazo[4,5-f]pyridine (PhIP) were used to purify by immunoaffinity these known mutagens and cross-reacting structural analogs from well-done cooked beef and urine samples. Materials recovered from the immunoaffinity columns were subsequently separated by HPLC to purify the known mutagens from cross-reacting chemicals that co-purify by immunoaffinity. Immunoaffinity chromatography was found to be a rapid means of quantifying individual known mutagens, with a minimum of precolumn sample clean-up required. In addition, this procedure has yielded several new mutagens present in cooked meats that are apparently structural analogs of PhIP. Immunoaffinity techniques were also used to purify metabolites from the urine of rats and humans exposed to MeIQx or PhIP. For MeIQx-exposed rats, the combination antibodies immunoconcentrated 75% of the total urinary radioactivity. Analysis of PhIP metabolites recovered from antibody columns is facilitated by the intrinsic fluorescence of PhIP and its metabolites, providing sufficient sensitivity to monitor individuals for the levels of PhIP excreted following consumption of typical western diets.

Animals↗