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Biomedical subjects

J M Park

Publications and source records attributed to J M Park.

At least 19 recordsLinked to original sources
PubMed2000

Metaplastic carcinoma of the breast: mammographic and sonographic findings.

PURPOSE: We investigated the mammographic, sonographic, and pathologic findings in metaplastic carcinoma of the breast. METHODS: The mammographic (n = 16) and sonographic (n = 11) findings in 16 patients with metaplastic carcinoma of the breast were analyzed retrospectively along with pathologic findings. Whenever possible, results of preoperative fine-needle aspiration biopsy and immunohistochemical studies were obtained. RESULTS: All patients presented with a palpable breast mass. The mean size of the lesions at pathologic examination was 4.2 cm. On mammography, 15 patients had a mass (1 patient had 2 masses), and 1 patient had only clustered microcalcifications without an associated mass. The mean longest diameter of the 16 masses on mammography was 4.6 cm. Eleven lesions (69%) were round to ovoid in shape, 13 lesions (81%) showed ill-defined or obscured margins, and 10 lesions (63%) showed associated architectural distortion. On sonography, 6 (55%) of 11 lesions were round to ovoid, 9 lesions (82%) had well-defined margins, and 6 lesions (55%) showed complex echogenicity with solid and cystic components. At pathologic examination, 4 of these 6 lesions showed hemorrhagic or cystic necrosis. Axillary lymph nodes were positive in 6 (40%) of 15 patients in whom axillary node dissection was performed. CONCLUSIONS: Metaplastic carcinoma of the breast manifests as a rapidly growing, mammographically ill-defined round mass with associated architectural distortion on mammograms. Complex echogenicity with solid and cystic components may be seen sonographically and is related to hemorrhagic or cystic necrosis seen pathologically.

Adult↗
PubMed2000

Clustering of breast microcalcifications: revisited.

AIM: To verify the diagnostic value of the traditional definition of 'clustering' of microcalcifications (more than five in the area of 1 cm(2)or 1 cm(3)) on mammography in the differential diagnosis of benign and malignant breast disease. METHODS AND MATERIALS: Three radiologists without knowledge of the final pathology retrospectively counted the number of microcalcifications per 0.25 cm(2) (0.5 x 0.5 cm) unit area on mammography in 57 pathologically proven non-palpable lesions including 26 cancers and 31 benign diseases. Pleomorphism of the microcalcifications, associated architectural distortion or mass or increased density and distribution of microcalcifications were also evaluated. RESULTS: The mean numbers of microcalcifications per 0.25 cm(2) were 16.4 in malignant and 16.7 in benign diseases (no statistically significant difference between the two groups). Pleomorphism of the microcalcifications, associated architectural distortion or mass or increased density were, however, important determining parameters. Clustering was more frequently observed in benign diseases. CONCLUSION: In this study, the mean number of microcalcifications per unit area is much larger than the traditional definition of 'clustering' and clustering itself is not effective in the differential diagnosis of benign and malignant breast lesions. Imaging features other than numbers of calcification per unit area are more important in assessing the significance of mammographic clustered microcalcifications.

Adult↗
PubMed2000

Localized multiple glomus tumors of the face and oral mucosa.

We describe a 54-year-old patient with an unusual localization of localized multiple glomus tumors. She had several nodules on the left mandibular area, lower lip, and anterior part of the buccal mucosa. A biopsy taken from the left mandibular area showed cystically dilated vessels lined by endothelial cells and a few outer layers of glomus cells in the dermis to subcutis. Localized multiple glomus tumors are rare, and both their facial and oral mucocal localization are extremely rare.

Actins↗
PubMed2000

Metallic punctate densities in the breast after Chinese herbal treatment: mammographic findings.

PURPOSE: To describe the mammographic features of metallic punctate densities seen in women who were treated with the herb go-yak for breast abscess and to explain the cause of these findings. MATERIALS AND METHODS: Mammograms showing metallic punctate densities that appeared to be microcalcifications in 34 women were analyzed retrospectively with attention to the location, shape, distribution, and depth of the lesions. In all patients, go-yak was applied into the open wound after abscess drainage 6-42 years before mammography. In six patients, histopathologic specimens were obtained after needle localization. RESULTS: Metallic densities were in the subareolar or central breast in 24 (71%) of 34 patients. The shape was predominantly round or punctate in all patients, but rod-shaped or linear lesions were found in seven patients. The distribution and depth of lesions were variable, but they extended to the subcutaneous fat in 29 patients (85%). A high concentration of lead was found in the histopathologic specimens and herb samples. CONCLUSION: Lead deposits associated with go-yak treatment should be included in the differential diagnosis when the suspected microcalcifications are of unusually high density, are central in location, and extend into the subcutaneous fat in Asian women with a history of breast abscess.

Abscess↗
PubMed2000

Self-treatment of obsessive-compulsive disorder guided by manual and computer-conducted telephone interview.

While on a waiting list for treatment by therapist-guided exposure and ritual prevention (ERP), patients with obsessive-compulsive disorder (OCD) did self-treatment at home guided by a manual plus a computer-driven telephone interview system (BT STEPS). Of 21 patients who used the system for at least three weeks while on the waiting list, one improved so much that subsequent therapist-guided ERP was unnecessary. Progress of the rest with the system predicted later progress with therapist-guided ERP. Improvement after using the system was similar to that of 20 matched historical controls who had had therapist-guided ERP without the prior use of BT STEPS. Outpatient users of BT STEPS needed less subsequent clinician-guided time than did their matched controls. In this pilot study, patients with OCD improved nearly as much with home self-treatment guided by a manual plus computer, as with treatment guided by a behaviour therapist.

Adult↗
PubMed2000

Metastatic tumors to the breast: mammographic and ultrasonographic findings.

We evaluated the mammographic (n = 16) and ultrasonographic (n = 15) findings of 18 patients with metastatic breast carcinoma. Fifteen patients showed multiple or diffuse lesions and three patients showed single lesions. Ten patients (55.6%) had bilateral lesions. Mammography revealed high density (15 cases, 93.8%), round to oval (11 cases, 68.8%) lesions with poorly defined or obscured margins (12 cases, 75.0%). No associated calcification was found in any lesion. Ultrasonographically, poorly defined (8 cases, 53.3%), irregularly shaped (8 cases, 53.3%), hypoechoic (14 cases, 93.3%), heterogeneous (8 cases, 53.3%) lesions were predominantly distributed superficially (11 cases, 73.3%). Axillary lymphadenopathy was detected in six patients (33.3%). The longest diameter of most of the lesions was less than 2.0 cm (13 cases, 81.3%). We conclude that metastatic tumors to the breast appear as relatively small, superficially located, poorly defined, irregular nodules without calcification on mammography and ultrasonography. However, when the metastatic lesion is diffuse, the appearance is indistinguishable from that of inflammatory breast carcinoma.

Adolescent↗
PubMed2000

Identification of H-2K(b)-restricted T-cell epitopes within the nucleocapsid protein of Hantaan virus and establishment of cytotoxic T-cell clones.

Although neutralizing antibodies against Hantaan virus (HTV) can protect hosts from viral infection, T-cell responses to HTV are also important in host defense against HTV. However, much less is known about cytotoxic T lymphocyte (CTL) responses to HTV. To identify CTL epitopes in the HTV nucleocapsid protein (NP), we selected 7 H-2K(b)-motif-fitting peptides. Of these peptides, 3 peptides (NP3, NP4, and NP7) were recognized by CTL responses derived from HTV-immunized mouse splenocytes. NP3 and NP4 peptides were also recognized by HTV-immunized splenocytes after secondary in vitro stimulation with the relevant peptide, but NP7 could not be recognized after in vitro stimulation. These results agree well with peptide immunization studies showing that peptide-specific CTL responses could be induced with NP3 and NP4 but not with NP7 peptide. Furthermore, CTL activity assay using targets, prepared to express the antigen (NP) endogenously, demonstrated that NP3 and NP4 peptides could be presented endogenously. CTL elicited with NP4 peptide retained some cross-reactivity and was difficult to long-term culture. However, NP3-elicited CTL was very specific for NP3 peptide and was stable enough to be cloned. Among many CTL lines elicited with HTV or HTV NP peptides, 6 NP3-specific CTL clones were established and have been maintained more than 2 years. All 6 CTL clones were characterized to be CD3+, CD4-, CD8+, CD25+, CD62L-, and NK1.1-, and to use TCR Vbeta6. This preferential usage of TCR Vbeta6 indicates that TCR Vbeta6 regions are important for recognition of the HTV NP3 epitope (NP221-228, SVIGFLAL) on H-2K(b) molecule. Our data demonstrate the definition of mouse CTL epitopes in HTV and the generation of HTV-specific mouse CTL clones.

Animals↗
PubMed1999

Caenorhabditis elegans mediator complexes are required for developmental-specific transcriptional activation.

Mediator proteins are required for transcriptional regulation of most genes in yeast. Mammalian Mediator homologs also function as transcriptional coactivators in vitro; however, their physiological role in gene-specific transcription is not yet known. To determine the role of Mediator proteins in the development of complex organisms, we purified putative Mediator complexes from Caenorhabditis elegans and analyzed their phenotypes in vivo. C. elegans Mediator homologs were assembled into two multiprotein complexes. RNA interference assays showed that the CeMed6, CeMed7, and CeMed10/CeNut2 gene products are required for the expression of developmentally regulated genes, but are dispensable for expression of the ubiquitously expressed genes tested in this study. Therefore, the gene-specific function of Mediator as an integrator of transcriptional regulatory signals is evolutionarily conserved and is essential for C. elegans development.

Amino Acid Sequence↗
PubMed1999

Neural network modeling for on-line estimation of nutrient dynamics in a sequentially-operated batch reactor.

In monitoring and controlling wastewater treatment processes, on-line information of nutrient dynamics is very important. However, these variables are determined with a significant time delay. Although the final effluent quality can be analyzed after this delay, it is often too late to make proper adjustments. In this paper, a neural network approach, a software sensor, was proposed to overcome this problem. Software sensor refers to a modeling approach inferring hard-to-measure process variables from other on-line measurable process variables. A bench-scale sequentially-operated batch reactor (SBR) used for advanced wastewater treatment (BOD plus nutrient removal) was employed to develop the neural network model. In order to improve the network performance, the structure of neural network was arranged in such a way of reflecting the change of operational conditions within a cycle. Real-time estimation of PO3-(4), NO-3, and NH+4 concentrations was successfully carried out with the on-line information of the SBR system only.

Anaerobiosis↗
PubMed1999

Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease.

Microtubule-associated protein tau in cerebrospinal fluid (CSF) has been proposed as a diagnostic marker for Alzheimer's disease (AD), but there is overlap between AD patients and non-AD controls. To improve the diagnostic accuracy, we measured phosphorylated tau in CSF, because phosphorylated tau accumulates as pathological paired helical filaments in neurons of the AD brain. Immunoblot showed that CSF contained a 32 kDa N-terminal fragment of tau that was partially phosphorylated on Ser199, Thr231 and Ser235. A sandwich enzyme immunoassay revealed that phosphorylated CSF-tau levels were significantly higher in AD patients than those in non-AD controls. Discrimination between the two groups was clearer in phosphorylated CSF-tau than in total CSF-tau. The data indicate that elevated phosphorylated CSF-tau level is a more specific diagnostic marker for AD.

Alzheimer Disease↗
PubMed1999

Design and synthesis of potent and selective 5,6-fused heterocyclic thrombin inhibitors.

Thrombin, a serine protease, plays a central role in the initiation of thrombotic events. We report the design, synthesis, and antithrombotic efficacy of XU817 (7), a nonpeptide 5-(amidino) indole thrombin inhibitor. Utilizing the co-crystal structure of XU817 bound in the active site of thrombin we were able to synthesize analogs with enhanced thrombin affinity.

Amidines↗
PubMed1999

Recruitment of TBP or TFIIB to a promoter proximal position leads to stimulation of RNA polymerase II transcription without activator proteins both in vivo and in vitro.

Eukaryotic transcriptional activators may function, at least in part, to facilitate the assembly of the RNA polymerase II (pol II) preinitiation complex at the core promoter region through their interaction with a subset of components of the basal transcription machinery. Previous studies have shown that artificial tethering of TATA-binding protein (TBP) to the promoter region is sufficient to stimulate pol II transcription in yeast. To test whether this phenomenon is a general one in eukaryotic pol II transcription, the DNA-binding domain of yeast GAL4 was fused to either Xenopus laevis TBP or TFIIB in order to enable these factors to be efficiently positioned near the transcription start site in a GAL4-binding site-dependent manner. We found that GAL4-xTBP as well as GAL4-xTFIIB directed an increased level of transcription without involvement of the transcriptional activator, suggesting that incorporation of these basal factors into a preinitiation complex (PIC) is a major rate-limiting step accelerated by activator proteins in metazoans. These results show that transcription activation by artificial recruitment of basal transcription machinery can be observed in general among eukaryotic transcription both in vivo and in vitro. Furthermore, failure of recovery of transcription by adding GAL4-xTFIIB after depletion of endogenous TBP with TATA oligo competitor suggests that recruitment of TBP cannot be bypassed for Pol II transcription.

Animals↗
PubMed1999

Oxybutynin chloride inhibits proliferation and suppresses gene expression in bladder smooth muscle cells.

PURPOSE: We test the hypothesis that oxybutynin chloride inhibits bladder smooth muscle cell proliferation. MATERIALS AND METHODS: Cultured rat bladder smooth muscle cells were grown in Medium 199 supplemented with 10% fetal bovine serum in the presence of 0, 1, 10 and 100 microM. oxybutynin. Cell proliferation was assessed by counting cell numbers 48 and 96 hours after plating. To investigate the role of oxybutynin in bladder smooth muscle cell proliferation after mechanical stretch, cells were grown on silicone elastomer bottomed culture plates and subjected to cyclical stretch-relaxation for 48 hours in the presence of 10 microM. oxybutynin. Deoxyribonucleic acid synthesis was assessed by tritiated thymidine incorporation assay. To examine the effect of oxybutynin on stretch activated gene expression, bladder smooth muscle cells were subjected to stretch-relaxation for 2 hours with and without 10 microM. oxybutynin, and relative c-jun messenger (m) ribonucleic acid (RNA) levels were assessed by semiquantitative reverse transcriptase-polymerase chain reaction with normalization to glyceraldehyde-3-phosphate dehydrogenase mRNA levels. RESULTS: The serum stimulated increase in bladder smooth muscle cell growth was inhibited by oxybutynin in a dose dependent manner. In bladder smooth muscle cells there was a 4.7-fold increase in deoxyribonucleic acid synthesis after mechanical stretch, which decreased by 40% (p <0.01) when cells were stretched in the presence of oxybutynin. Stretch stimulated significant increase in c-jun mNRA levels, which was significantly decreased by oxybutynin. CONCLUSIONS: Oxybutynin chloride inhibits bladder smooth muscle cell proliferation induced by serum and mechanical stretch. A potential mechanism by which oxybutynin inhibits proliferation may be the down regulation of growth promoting genes, such as c-jun. We speculate that oxybutynin may be useful for preventing permanent hypertrophic bladder changes in addition to decreasing intravesical pressure.

Animals↗
PubMed1999

Renal renin-angiotensin system dysregulation caused by partial bladder outlet obstruction in fetal sheep.

BACKGROUND: To determine whether fetal renal obstruction activates the renal renin-angiotensin system (RAS), an important mediator in normal kidney development and obstructive nephropathy, we used a model of fetal partial bladder outlet obstruction (PBOO). METHODS: Total RNA and protein was extracted from kidney of sheep fetuses with partial bladder outlet obstruction created at 95 days gestation, after 2 (N = 6) and 5 weeks of obstruction (term; N = 6), and from normal fetal sheep at various time points between 60 and 135 days of gestation (total N = 19). Relative levels of mRNA for renin, angiotensinogen, type 1 and 2 angiotensin II (Ang II) receptors (AT-1 and AT-2), and transforming growth factor-beta1 (TGF-beta1) were assessed by semiquantitative reverse transcription-polymerase chain reaction. Expression levels of AT-2 receptor protein were measured by Western blot analysis. RESULTS: Renin mRNA expression was increased (250%) after two weeks of obstruction. In normal fetuses, AT-1 expression was low at 60 to 75 days of gestation and increased toward the end of gestation, whereas AT-2 expression showed a reversed pattern. At 109 days, PBOO caused an increased expression of AT-2 mRNA compared with normals (400%). Correspondingly, AT-2 receptor protein was more abundant in obstructed kidneys. TGF-beta1 mRNA expression was significantly increased in obstructed kidneys at 109 days gestation. CONCLUSIONS: These observations confirm the reciprocal developmental regulation of AT-1 and AT-2 receptors' expression, suggesting their functional role in renal development. Partial bladder outlet obstruction produces specific alterations: increased renin expression and altered balance of receptor subtypes, which may induce altered functional and vascular regulation of the obstructed fetal kidney. TGF-beta1, a mediator of Ang II-induced fibrosis, may play a role in inducing and propagating interstitial fibrosis.

Animals↗
PubMed1999

Murine endotoxin-induced uveitis, but not immune complex-induced uveitis, is dependent on the IL-8 receptor homolog.

PURPOSE: To determine the roles of the murine interleukin-8 receptor homolog (mIL-8Rh, neutrophil chemokine CXC receptor 2) and macrophage inflammatory protein-1alpha (MIP-1alpha, a CC chemokine) in two eye inflammation models: endotoxin-induced uveitis (EIU) and immune complex-induced uveitis (reverse passive Arthus reaction (RPAR) uveitis). METHODS: For the EIU model, 250 ng E.coli endotoxin was injected into the vitreous of mIL-8Rh-/- mice or heterozygous littermate mIL-8Rh+/- controls and into MIP-1alpha-/- mice or congenic MIP-1alpha+/+ controls. Eyes were harvested after 24 h for histologic characterization of infiltrating cells and IL-6 bioassays. For the RPAR model, mouse antiserum against human serum albumin (HSA) was injected into the vitreous of mIL-8Rh-/-, mIL-8Rh+/-, MIP-1alpha-/-, and MIP-1alpha+/+ mice. Twenty-four hours later, animals were challenged with intravenous HSA. Eyes were harvested after 4 h for analysis. RESULTS: RPAR resulted in the deposition of immune complexes at the ciliary area and iris with the subsequent development of uveitis. Genetic deficiency of mIL-8Rh reduced the median number of infiltrating cells in EIU by 63% (p < 0.01) but had no effect on RPAR-induced inflammation. In the EIU model, macrophages comprised a much higher percentage (45%) of infiltrating cells in mice lacking mIL-8Rh than in controls (17%). Loss of the MIP-1alpha gene had no apparent effect on RPAR uveitis and a 39% reduction of infiltrating cells in EIU that was not statistically significant. IL-6 activity in aqueous humor was much less in mice with RPAR uveitis than in those with EIU. Neither gene deletion had a significant impact on IL-6 levels in either disease model. CONCLUSIONS: Chemokines acting via mIL-8Rh have a significant role in the induction of neutrophil infiltration during EIU but not during RPAR uveitis. MIP-1alpha is not critical for either EIU or RPAR-induced uveitis. The differential dependence on IL-8-like chemokines is in accord with the two forms ofuveitis having different etiologies and, therefore, potentially different optimal therapies.

Animals↗
PubMed1999

Assessment of novel anti-p185HER-2 monoclonal antibodies for internalization-dependent therapies.

Novel therapies that require internalization of effector domains may be improved by assessing the efficacy of postbinding receptor-mediated endocytosis. To achieve targeted gene therapy of immunotoxin therapy, natural vector-host tropisms must be altered. Recent improvements in monoclonal antibody (MAb) engineering have expanded the potential range of host cells that can be targeted for therapeutic intervention. However, relatively little is known about cellular responses after binding of a vector construct. We have tested the utility of four novel MAbs recognizing the extracellular domain of p185HER-2, a membrane receptor protein, for use in internalization-dependent therapies. All four antibodies bound to p185HER-2 in a number of immunoassays. Two antibodies recognized accessible epitopes of p185HER-2 on viable cells. Radioimmunoassay demonstrated that antibody-membrane receptor complexes formed by two antibodies were internalized and trafficked through an endolysosomal degradative pathway. Two of the four antibodies evaluated were found to have favorable internalization characteristics suitable for incorporation in a targeting vector. This analytical approach could be applied to antibodies prior to and after fusion with various vectors or toxins to determine the potential utility of the antibodies for targeted therapy.

Animals↗
PubMed1999

An activator binding module of yeast RNA polymerase II holoenzyme.

The Mediator complex of Saccharomyces cerevisiae is required for both general and regulated transcription of RNA polymerase II (PolII) and is composed of two stable subcomplexes (Srb4 and Rgr1 subcomplexes). To decipher the function of each Mediator subcomplex and to delineate the functional relationship between the subcomplexes, we characterized the compositions and biochemical activities of PolII-Mediator complexes (holoenzymes) prepared from several Mediator mutant strains of S. cerevisiae. We found that holoenzymes devoid of a functional Gal11 module were defective for activated but not basal transcription in a reconstituted in vitro system. This activation-specific defect was correlated with a crippled physical interaction to transcriptional activator proteins, which could be bypassed by artificial recruitment of a mutant holoenzyme to a promoter. Consistent with this observation, a direct interaction between Gal11 and gene-specific transcriptional activator proteins was detected by far-Western analyses and column binding assays. In contrast, the srb5 deletion mutant holoenzyme was defective for both basal and activated transcription, despite its capacity for activator binding that is comparable to that of the wild-type holoenzyme. These results demonstrate that the Gal11 module of the Rgr1 subcomplex is required for the efficient recruitment of PolII holoenzyme to a promoter via activator-specific interactions, while the Srb4 subcomplex functions in the modulation of general polymerase activity.

DNA-Binding Proteins↗