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Biomedical subjects

M W Lee

Publications and source records attributed to M W Lee.

At least 19 recordsLinked to original sources

Disseminated microsporidiosis in a renal transplant recipient.

Disseminated microsporidiosis is diagnosed uncommonly in patients not infected with human immunodeficiency virus (HIV). We present a case of disseminated microsporidiosis in a renal transplant recipient who was seronegative for HIV. Chromotrope-based stains were positive for microsporidia in urine, stools, sputum, and conjunctival scrapings. Electron microscopy, immunofluorescence, polymerase chain reaction, and cultures of renal tissue identified the organism as Encephalitozoon cuniculi. The patient was treated with oral albendazole and topical fumagillin with clinical improvement. In addition, she underwent a transplant nephrectomy and immunosuppressive therapy was withdrawn. Follow-up samples were negative for microsporidia. However, the patient developed central nervous system manifestations and died. An autopsy brain tissue specimen demonstrated E. cuniculi by immunofluorescent staining. Disseminated microsporidiosis must be considered in the differential diagnosis of multiorgan involvement in renal allograft recipients.

Animals↗

CD30-positive T-cell-rich pseudolymphoma induced by gold acupuncture.

Cases of pseudolymphoma induced by intradermal gold injection or gold piercing have previously been described. Most of these cases showed the histopathological finding of B-lymphocyte predominant lymphocytoma cutis. We describe a patient with gold acupuncture-induced T-cell-rich pseudolymphoma. Some T cells showed positive staining with CD30. The lesions responded to an intralesional injection of triamcinolone acetonide.

Acupuncture Therapy↗

Delivering adjuvant chemotherapy to women with early-stage breast carcinoma: current patterns of care.

BACKGROUND: Variations in practice patterns are markers for the quality of patient care in general medicine, but little is known about variation in care delivered to cancer patients. This study's purpose was to describe chemotherapy use, variations in chemotherapy delivery, and the incidence of complications in community practice settings. METHODS: Data describing adjuvant chemotherapy for patients with early-stage breast carcinoma (ESBC) were collected from an ongoing Oncology Practice Pattern Study at 13 large managed care, academic, and community practices (1111 patients). Data collection included information about diagnoses and adjuvant chemotherapy treatments, laboratory results, supportive care, complications, and treatment modifications. RESULTS: The median patient age was 50 years, and most patients had zero to three positive lymph nodes. Chemotherapy regimens consisting of cyclophosphamide, methotrexate, and 5-fluororacil (CMF) and of doxorubicin and cyclophosphamide (AC) accounted for 76% of the adjuvant therapies used. Overall, 30% of patients had delivered average relative dose intensities </= 85% of the referenced targets. Delivered summation dose intensities (SDIs) frequently were well below targeted SDIs. Neutropenia-related dose modifications occurred for 27.6% of patients and recurred with a 60.7% rate. AC was the regimen delivered with a dose intensity closest to the referenced target. However, patients who were treated with AC regimens and with regimens consisting of cyclophosphamide, doxorubicin, and 5-fluorouracil had significantly higher rates of chemotherapy-related complications compared with patients who were treated with CMF regimens in the most recent treatment years. CONCLUSIONS: Adjuvant chemotherapy for patients with ESBC frequently is not administered as referenced in off-protocol community settings. Variation in the delivered SDI raises concerns about potential treatment outcomes and warrants strategies to identify patients who are at risk for complications early in therapy.

Adult↗

Estrogen attenuates cell death induced by carboxy-terminal fragment of amyloid precursor protein in PC12 through a receptor-dependent pathway.

In the present study, we investigated effects of estrogen on cell death induced by carboxy-terminal fragment of amyloid precursor protein (CT), a candidate causative substance in the pathogenesis of Alzheimer's disease. 17 beta-Estradiol attenuated CT-induced cell death in PC12 cells, whereas 17 alpha-estradiol, nonestrogenic stereoisomer, did not exert any significant protective effect on CT-induced cell death. These results suggest that protective effects of estrogen may be mediated by estrogen receptor (ER) in PC12 cells. To confirm the results, we determined the effects of tamoxifen, an estrogen receptor antagonist. Tamoxifen blocked the protective effects of 17 beta-estradiol, although it did not affect those of 17 alpha-estradiol. Overall, it might be thought that the protective effect of estradiol on CT-induced cell death is achieved by hormonal properties mediated through the estrogen receptor rather than the structural properties as a reducing agent.

Alzheimer Disease↗

The protective role of HSP90 against 3-hydroxykynurenine-induced neuronal apoptosis.

3-hydroxykynurenine (3HK), an endogenous metabolite of tryptophan in the kynurenine pathway, is a potential neurotoxin in several neurodegenerative disorders. Stabilizing protein structure, heat shock proteins (HSPs) have diverse roles as molecular chaperones to mediate stress tolerance. In the present study, we investigated the possible protective role of HSPs against 3HK induced neuronal cell death. Here we report that 3HK induced in a dose- and time-dependent manner neuronal cell death in neuroblastoma SK-N-SH cells. The cell death showed characteristic apoptotic features such as cell shrinkage, plasma membrane blebbing, chromatin condensation, and nuclear condensation and fragmentation. Furthermore, SK-N-SN cells were protected from 3HK induced cytotoxicity by prior elevation of HSPs expression. Our results show that the protective effect was abolished by HSP90 anti-sense oligonucleotides while not by HSP27 and HSP70 anti-sense oligonucleotides. Also, our result shows that HSP90 effectively inhibits caspases activities leading to the apoptosis. These results suggest that 3HK induces apoptosis in neuroblastoma SK-N-SN cells and that HSP90 is major contributing protein component of protection against 3HK induced apoptosis.

Apoptosis↗

Composite control of a gyro mirror line-of-sight stabilization platform--design and auto-tuning.

In this paper, we propose a composite control scheme for a gyro mirror line-of-sight stabilization system. It comprises of an adaptive controller augmented with a variable structure (VS) to remain efficient in the face of modeling errors and extraneous disturbances. Under an adequate selection of control parameters, the control scheme guarantees an asymptotically stable closed-loop response. An automatic tuning method is developed for the proposed control scheme which explicitly uses inherent properties of the control structure for tuning purposes. Simulation and experimental results are provided to illustrate the operational principles of the proposed scheme and to demonstrate its viability in real practical applications.

Journal Article↗

C-terminal fragment of amyloid precursor protein induces astrocytosis.

One of the pathophysiological features of Alzheimer's disease is astrocytosis around senile plaques. Reactive astrocytes may produce proinflammatory mediators, nitric oxide, and subsequent reactive oxygen intermediates such as peroxynitrites. In the present study, we investigated the possible role of the C-terminal fragment of amyloid precursor protein (CT-APP), which is another constituent of amyloid senile plaque and an abnormal product of APP metabolism, as an inducer of astrocytosis. We report that 100 nM recombinant C-terminal 105 amino acid fragment (CT105) of APP induced astrocytosis morphologically and immunologically. CT105 exposure resulted in activation of mitogen-activated protein kinase (MAPK) pathways as well as transcription factor NF-kappaB. Pretreatment with PD098059 and/or SB203580 decreased nitric oxide (NO) production and nuclear factor-kappa B (NF-kappaB) activation. But inhibitors of NF-kappaB activation did not affect MAPKs activation whereas they abolished NO production and attenuated astrocytosis. Furthermore, conditioned media derived from CT105-treated astrocytes enhanced neurotoxicity and pretreatment with NO and peroxynitrite scavengers attenuated its toxicity. These suggest that CT-APP may participate in Alzheimer's pathogenesis through MAPKs- and NF-kappaB-dependent astrocytosis and iNOS induction.

Amyloid beta-Protein Precursor↗

A novel jasmonic acid-inducible rice myb gene associates with fungal infection and host cell death.

Endogenous signal molecules such as jasmonic acid (JA) and salicylic acid (SA) play an important role in induced resistance against pathogen infection and insect herbivory. In rice seedlings, JA is an effective inducer of systemic acquired resistance (SAR) against infection of blast fungus (Pyricularia grisea). To gain further insights into JA-mediated defense signaling pathways, we isolated and characterized a pathogen- and JA-induced rice gene (JAmyb) that encodes a Myb transcription factor. The JAmyb gene was induced within 1 day after fungal infection in resistant and susceptible interactions prior to lesion formation. Unlike most defense-related genes that are activated faster and stronger in resistant interactions, JAmyb induction by blast fungus is much higher in susceptible interactions, accompanied by large lesions and extensive tissue damage. Significant induction of JAmyb also was observed during cell death and lesion formation in certain lesion mimic mutants. Interestingly, JAmyb was activated rapidly by JA or wounding, independent of de novo protein synthesis, but not by other endogenous signal molecules such as SA and abscisic acid or SAR inducers such as benzothiadiazole and probenazole. We used SA-deficient transgenic plants to further demonstrate that depletion of SA in rice did not abolish but rather enhanced blast-induced JAmyb expression. These results suggest that JAmyb is related closely to host cell death and is involved in the JA-mediated, SA-independent signaling pathways in rice.

Amino Acid Sequence↗

Identification of defense-related rice genes by suppression subtractive hybridization and differential screening.

Identification of host genes involved in defense responses is one of most critical steps leading to the elucidation of disease resistance mechanisms in plants. In this study, two different cloning strategies were employed to identify defense-related genes from a tropical japonica rice cultivar (Oryza sativa cv. Drew). With the use of bacterial colony arrays, differential screening of a blast fungus (Pyricularia grisea)-induced rice cDNA library led to the isolation of 22 distinct rice genes that are expressed differentially in response to blast infection. Sequence analysis indicates that most of them are full-length cDNAs encoding pathogenesis-related proteins or other relatively abundant proteins. In combination with treatments of cycloheximide plus jasmonic acid (JA) or benzothiadiazole (BTH) in rice seedlings, the polymerase chain reaction-based suppression subtractive hybridization also was conducted to search for immediate early (IE) defense-related genes whose transcription is independent of de novo protein synthesis. The initial screening of only 768 subtracted clones resulted in the identification of 34 distinct IE genes that are induced by JA, BTH, and/or blast infection. Database searches revealed that these IE genes encode putative mitogen-activated protein kinase, diacylglycerol kinase, zinc finger protein, RelA-SpoT protein, ankyrin-containing protein, ABC transporter, beta-ketoacyl-CoA synthase, and other potential defense-signaling components. Further characterization of these novel IE genes will likely facilitate the elucidation of defense signal transduction in rice plants.

Cycloheximide↗

Morphologic expressions of urothelial carcinoma in situ: a detailed evaluation of its histologic patterns with emphasis on carcinoma in situ with microinvasion.

The recently proposed World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification of flat urothelial lesions expands the definition traditionally used for urothelial (transitional cell) carcinoma in situ (CIS), basing its diagnosis predominantly on the severity of cytologic changes. Lesions now encompassed within the diagnosis of CIS exhibit an array of cytologic and architectural features, which have not been documented in detail. In this study, cases were examined with respect to histologic patterns and microinvasion (invasion into the lamina propria to a depth of less than 2 mm). Five major patterns of CIS, often occurring in the same specimen (160 patterns in 77 cases), were noted. Common to each pattern was the presence of high-grade cytologic atypia, the definitional feature. The patterns found include 1) large cell CIS with pleomorphism (57%), in which the cells had abundant cytoplasm and nuclear pleomorphism; 2) large cell CIS without nuclear pleomorphism (48%); 3) small cell CIS (14%), in which the cytoplasm was relatively scant and pleomorphism was usually minimal; 4) clinging CIS (40%), in which the urothelium was denuded with a patchy, usually single layer of atypical cells; and 5) cancerization of urothelium (16%) with either pagetoid spread (clusters or isolated single cells) or undermining or overriding of the normal urothelium. Carcinoma in situ with microinvasion into the lamina propria (13 cases: 3 of 77 CIS cases studied above and 10 additional cases) was evident as invasive cells with retraction artifact mimicking vascular invasion (77%, 10 cases); nests, irregular cords, and strands, or isolated single cells with desmoplasia (8%, 1 case); or absent stromal response (15%, 2 cases). Although the diagnostic terminology for all of these patterns, for the purposes of the surgical pathology report, should be simply urothelial CIS with no specific mention of the morphologic pattern, awareness of the histologic diversity of CIS will facilitate the diagnosis of this therapeutically and biologically critical flat lesion of the urothelium. These lesions may be associated with microinvasion, which may be clinically unsuspected and histologically subtle.

Carcinoma in Situ↗

Antifungal activity of modified hederagenin glycosides from the leaves of Kalopanax pictum var. chinense.

Monodesmosides which were obtained from the partial degradation of hederagenin bisdesmosides exhibited significant antifungal effect against Microsporum canis, Coccidioides immitis, Trichophyton mentagrophytes, Cryptococcus neoformans, and Candida albicans at the minimal inhibitory concentrations of 6.25-25 microg/ml. The hederagenin glycosides were isolated from the leaves of Kalopanax pictum var. chinense.

Antifungal Agents↗

Histologic and histochemical characterization of seminal vesicle intraluminal secretions.

CONTEXT: We have observed intraluminal crystalloid morphology in seminal vesicles that is superficially similar to that seen in prostate neoplasia, but found little information on such morphology in the literature. DESIGN: Two hundred fifty-three prostate specimens (163 needle biopsies, 75 radical prostatectomies with prostate carcinoma, 11 prostates from autopsy, and 4 cystoprostatectomies without prostate carcinoma) were examined for seminal vesicle secretions, which were categorized as (a) dense platelike inspissated, (b) fluidlike, (c) crystalloid morphology, and (d) absent. Histochemical stains (periodic acid-Schiff with and without diastase, Alcian blue at pH 2.5, and mucicarmine) were performed to characterize the nature of secretions. RESULTS: Proteinaceous secretions were identified in 82% of seminal vesicles examined. Of these, 61% had predominantly dense, platelike, inspissated secretions, 15% had predominantly fluidlike secretions, and 24% had predominantly crystalloid morphology. Although in some cases the crystalloid morphology resembled that of prostatic intraluminal crystalloids, the seminal vesicle crystalloids differed in that they were invariably multiple, had curved edges, and had varied forms (elliptical, cylindrical, rodlike, and rectangular). Seventy-one percent of seminal vesicle crystalloids were associated with dense, platelike, inspissated secretions and appeared to be created by fracturing within platelike secretions. There was no relationship between seminal vesicle crystalloid morphology and associated malignancy in the prostate gland, as it was seen in 24% of cases with prostate carcinoma and 25% of cases without prostate carcinoma (P = 1.0000). Fluidlike secretions were positive for Alcian blue (pH 2.5) and mucicarmine, whereas dense platelike secretions and crystalloid morphology were negative for Alcian blue (pH 2.5) and mucicarmine. CONCLUSIONS: Seminal vesicle secretions are fairly common and, when fluidlike, are composed of acid mucopolysaccharides. Inspissation of secretions appears to be associated with loss of acidity, presumably resulting in dense platelike secretions and crystallization. Awareness of both the crystalloid morphology in seminal vesicle tissue and the distinguishing features from prostatic crystalloids may be important while interpreting prostate needle biopsies in which seminal vesicle epithelium may be confused for prostate carcinoma because of a small acinar morphology with accompanying cytologic atypia and crystalloid morphology.

Biopsy, Needle↗