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Biomedical subjects

M Cho

Publications and source records attributed to M Cho.

At least 55 records · Page 3Linked to original sources

E-cadherin and alpha-, beta- and gamma-catenin expression in prostate cancers: correlation with tumour invasion.

The E-cadherin-catenin complex plays an important role in establishing and maintaining intercellular connections and morphogenesis and reduced expression of its constituent molecules is associated with invasion and metastasis. In the present study, we examined E-cadherin and alpha-, beta- and gamma-catenin levels in tumour tissues obtained by radical prostatectomy in order to investigate the relationship with histopathological tumour invasion. Immunohistochemical findings for 45 prostate cancer specimens demonstrated aberrant expression of each molecule to be associated with dedifferentiation and, in addition, alteration of staining patterns for the three types of catenin was significantly correlated with capsular but not lymphatic or vascular invasion. The data thus suggest that three types of catenin may be useful predictive markers for biological aggressiveness of prostate cancer.

Aged↗

Expression of pepsinogen II with androgen and estrogen receptors in human prostate carcinoma.

The expression of pepsinogen II (PG II), an aspartyl proteinase usually involved in the digestion of proteins in the stomach, was immunohistochemically investigated in conjunction with androgen (AR) and estrogen receptor (ER) status in prostate adenocarcinomas. Of a total of 38 samples obtained from radical prostatectomies, 23 tumors (60.5%) were positive for PG II and there was a significant positive correlation to the expression of AR but not to ER. Cells positive for PG II were localized mainly to the peripheral zones of tumorous glands which, in normal prostate, are negative, and in areas also expressing AR. In addition, a significant correlation between AR and ER was detected in the prostate carcinomas examined, which suggests a hormone-dependent status. On the basis of these results, PG II expression might be closely related to hormonal alterations associated with the development of prostate tumors.

Adenocarcinoma↗

Fitting the log-F accelerated failure time model with incomplete covariate data.

Data obtained from studies in the health sciences often have incompletely observed covariates as well as censored outcomes. In this paper, we present methods for fitting the log-F accelerated failure time model with incomplete continuous and/or categorical time-independent covariates using the Gibbs sampler. A general location model that allows different covariance structures across cells is specified for the covariates, and ignorable missingness of the covariates is assumed. Techniques that accommodate standard assumptions of ignorable censoring as well as certain types of nonignorable censoring are developed. We compare our approach to traditional complete-case analysis in an application to data obtained from a study of melanoma. The comparison indicates that substantial gains in efficiency are possible with our approach.

Biometry↗

Immunohistochemical analysis of midkine expression in human prostate carcinoma.

Midkine (MK) is a growth/differentiation factor frequently expressed at high levels in some types of human malignancies. To investigate whether MK is a useful marker in prostate carcinogenesis, immunohistochemical analysis was performed on samples of both latent and clinical prostate cancers of various stages, as well as on specimens of normal gland and prostatic intraepithelial neoplasia (PIN). Of the 80 clinical cancers examined, 69 specimens (86.3%) were immunoreactive for MK, with metastatic lesions generally showing higher expression than the corresponding primaries; normal prostate tissues were negative or showed only weak staining. Midkine was also detected in 12 of 15 latent cancers (80%) and in 12 of 16 cases of PIN (75%). In sections of whole prostate, MK showed variable expression through tumorous sections, probably in reflection of heterogeneous cell populations. The results demonstrate the possible value of MK as a marker for early and latent disease, as well as for more advanced clinical stages of prostate cancer.

Aged↗

Genomic alterations in human meningiomas detected by restriction landmark genomic scanning and immunohistochemical studies.

Using restriction landmark genomic scanning (RLGS) methods, 21 samples of human meningioma were analyzed. We found 3 alterations in the genomic DNAs of tumor samples located on chromosomes 5, 14 and 17 which appear to be common to the meningothelial subtype. Two other separate genetic abnormalities located on chromosomes 9-12 and 20 are apparently associated with atypical meningiomas. In addition, the neurofibromatosis type 2 gene is apparently involved in more than half of the tumor samples. There appear to be both common and type-specific genetic mutations associated with the formation and progression of human meningiomas.

Adult↗

[A case of paraganglioma of the urinary bladder].

A 50-year-old male was referred to our department because of dysuria. On cystoscopy, a submucosal bladder tumor was seen at the posterior wall of the urinary bladder. Transurethral resection was performed with no intraoperative complications. Histopathological diagnosis of paraganglioma was confirmed by immunohistochemical staining.

Humans↗

Analysis of the envelope region of hepatitis G virus isolated from Korean patients.

The genetic diversity of hepatitis G virus (HGV) was investigated. By using a RT-PCR procedure, 14% of either HBV (hepatitis B virus)- or HCV (hepatitis C virus)-positive Korean hepatitis patients were proved to be HGV positives. Nucleotide sequences in the E1 region of the eight isolates from Korean patients and the six previously reported isolates were compared. Nucleotide substitutions spread uniformly throughout the E1 region. Sequence homology among the Korean isolates was 84-99% and 88-99% at the nucleotide and amino acid sequences, respectively, whereas those from different geographic areas was slightly lower at both levels. At least two genotypes might exist among the Korean HGV isolates. Compared to the corresponding region of HCV, the E1 sequence from HGV is moderately conserved. In addition, as frameshift mutations were observed in most of the Korean isolates compared to the prototype HGV sequence, the Korean isolates might not use the translational initiation site of the prototype HGV for polyprotein translation. Because a putative signal sequence of E1 for entry into endoplasmic reticulum starts from the N-terminus of the polyprotein, and capsid-like peptides composed of basic amino acids could not be detected from the upstream region of E1, the core protein of HGV is absent, or at least not present, at the region next to 5'-UTR. Therefore, HGV could be clearly distinguished from other genera of Flaviviridae.

Amino Acid Sequence↗

Formation of 8-hydroxydeoxyguanosine in rat kidney DNA after administration of N-ethyl-N-hydroxyethylnitrosamine.

N-Ethyl-N-hydroxyethylnitrosamine (EHEN) is known to induce renal and liver tumors in rodents. Recent reports have indicated the formation of 8-hydroxydeoxyguanosine (8-OHdG), an oxidative DNA product, induced by various carcinogens. In the present study, to examine whether oxygen radicals are involved in tumorigenesis induced by EHEN, we investigated the formation and localization of 8-OHdG in kidney, liver and lung of rats. The effects of reduced glutathione (GSH) and diethylmaleate on these responses were also studied. Multiple doses of EHEN administrations (250, 500 or 750 mg/kg, i.p.) resulted in a significant elevation of the 8-OHdG level in kidney DNA in a dose-dependent manner and the formation of 8-OHdG reached the maximal level at 1-2 h after EHEN injection and recovered to the control level at 4 h. On the other hand, no increase in the 8-OHdG level was observed in the DNA of liver and lung. Combined pre- and post-treatment of rats with 2 x 800 mg/kg of GSH i.p. inhibited the elevation of the 8-OHdG level induced by EHEN. Pre-treatment with 0.3 ml/kg of diethylmaleate i.p. increased the formation of 8-OHdG. In the immunohistochemical examinations of rats treated with EHEN (750 mg/kg, i.p.), nuclear expression of 8-OHdG was detected in the epithelial cells of renal cortex, while no induction was observed in liver and lung. These findings suggest that the formation of 8-OHdG by active oxygen species may be an important factor in the initiation of EHEN-induced kidney carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

Priming in the brain, an immunologically privileged organ, elicits anti-tumor immunity.

A crucial question in the study of tumor neuro-immunology concerns the capacity of the central nervous system to initiate and execute an immune response. In a 100% fatal rat malignant glioma model, genetically modified tumors secreting INF-gamma intracerebrally generate an immune response resulting in a substantial increase in survival time, tumor rejection and specific systemic immunity. Tumors modified to secrete IL-2 alone do not change the biologic behavior of transfected gliomas. INF-gamma induces elevated expression of major-histocompatibility-complex-class-I and -class-II molecules in microglia throughout the brain and invokes enhanced tumor infiltration by CD4, CD8 and NK cells. These findings demonstrate successful immunization against a central-nervous-system tumor by direct priming in the brain with a live growth-competent tumor vaccine.

Animals↗

Cholesterol efflux effect of high density lipoprotein is impaired by whole cigarette smoke extracts through lipid peroxidation.

It has been reported that high density lipoprotein (HDL) plays an anti-atherogenic role by stimulating cholesterol efflux from the foam cells in the atheromatous lesion. In this study, we prepared a novel modified form of HDL (CS-HDL) by incubating HDL with whole cigarette smoke (CS) extracts containing both particulate matter and gas-phase smoke, and examined its effect on cholesterol efflux. CS-HDL showed a marked increase of conjugated dienes and denaturation of apoA-I, a major protein component of HDL. The cholesterol efflux effect of CS-HDL was remarkably reduced to the same level as that of oxidatively modified HDL induced by copper ion (Ox-HDL). Addition of 20 microg/ml superoxide dismutase (SOD) during the CS-modification of HDL caused retrieval of cholesterol efflux activity by 53% and a remarkable decrease in the conjugated dienes level. SOD, however, had no ameliorative effect on apoA-I denaturation. When HDL was incubated only with gas-phase smoke (gasCS-HDL), neither increase of conjugated dienes nor impairment of the cholesterol efflux effect was observed, whereas apoA-I was denaturated to the same extent as seen in CS-HDL. These results indicate that whole CS-extracts, but not gas-phase smoke, reduces cholesterol efflux effect of HDL and that lipid peroxidation associated with superoxide anion is involved in this functional impairment.

Animals↗

Ossifying renal cell carcinoma.

In older children, ossifying renal cell carcinoma is a potential explanation for a network of well-organized, curvilinear high-attenuation areas in a renal mass. Since ossification of renal cell carcinoma is a favorable tumor marker that implies a less extensive resection, it is important to anticipate this tumor before surgical resection is undertaken.

Adolescent↗

Genomic aberrations in renal cell carcinomas detected by restriction landmark genomic scanning.

In order to reveal and characterise genetic events occurring in renal tumorigenesis, samples of sporadic renal cell carcinomas (RCCs) were examined using restriction landmark genomic scanning (RLGS), an electrophoretic separation technique which detects gene amplification and deletion. We were able to find two fragments frequently amplified and 10 others commonly showing reduced signal intensity within the 16 tumour samples analysed. These altered spots were located on chromosomes 2, 3, 9-12, 16, 17 and 18 according to chromosomal assigned RLGS. A subset of reduced fragments appeared to be correlated to tumour type and were located within a new chromosomal region, suggesting genetic specificity within the process of renal carcinogenesis.

Aged↗

Sequence analysis of the 5'-flanking region of the gene encoding human HOXA-7.

We have isolated and characterized the immediate 5'-flanking region (886 bp) of the gene encoding human HOXA-7. When the total sequence was compared with those of mice, 93% of the 3' 518 bp (nt 370-886) sequences were identical, in which the 245 bases just preceding the AUG initiator codon (nt 614) was as highly conserved as in the coding region (nt 614-886). Sequences further upstream (nt 1-370) by comparison were highly diverged. In the 245 bp region, 8 stop and 3 initiation (including the initiator) codons were located, and a 50-aa long presumptive polypeptide was encoded. Nucleotide sequence analysis revealed three Sp1 and one AP2 binding sites, as well as one CAAT box. However, there was no consensus sequence for a TATA box in the 5' flanking region. One RARE repeat, one krox20 and three Hox-PBC binding sites were detected. Since many of the factor recognition sites were located in the immediate 5' flanking sequences of a highly-conserved region, it might be speculated that a regulatory mechanism for Hox gene expression is conserved throughout the evolution and one possible mechanism could be at the post-translational level.

5' Untranslated Regions↗

Genomic structure and sequence analysis of human HOXA-9.

In order to understand the regulatory mechanisms establishing and maintaining HOXA-9 gene expression, structural information about the gene is a prerequisite. Therefore, we sequenced the 7.2-kb region of the human HOXA-9 gene and mapped the positions of two partial cDNAs consisting of one of two 5' exons, AB (358 bp) or CD (568 bp), and a common 3' exon (exon II), which are separated by 5.4- and 1.0-kb introns, respectively. When the amino acid sequence homologies were compared with those of other Hox genes belonging to the same paralogous group, exon CD exhibited the strongest homology: 73% of 91 aa residues exactly matched those of chicken Hoxa-9. An intermediate exon (90 bp) was detected within exon CD. It was surrounded by a splice acceptor and a donor at both the 5' and 3' ends, and one branchpoint site was found near the splice-acceptor site. Nucleotide sequence analysis along this region revealed two TATA boxes, one CAAT box, one GC box, and one each of the following binding sites--engrailed, eve-stripe2-hb3, and Krox20--just upstream of exon CD. A CpG island and two RARE repeats were detected within intron I. Northern blot analysis showed that at least four main transcripts were generated along this region: all fetal tissues tested (brain, lung, liver, and kidney) produced a 1.8-kb homeobox-containing transcript (HA-9A); a 2.2- and a 3.3-kb transcript were generated from exon CD and exon II (HA-9B), especially in fetal and adult kidneys as well as in adult skeletal muscle; the 1.0-kb transcript was likely to be generated by the intermediate exon in all adult and fetal tissues. Several weak bands without tissue specificity were likely to be contributed by the hybrid transcripts between HOXA-9 and the other HOXA gene(s). Together, these results may account for the unique degree of conservation of the HOX cluster in general.

Adult↗

Physicians' attire as perceived by young children and their parents: the myth of the white coat syndrome.

OBJECTIVE: To determine if young children have a preference regarding whether physicians do or do not wear a white coat. METHODS: One hundred one children, ages four to eight years, and their parents were recruited from the outpatient setting of a pediatric referral center. Two pairs of photographs, the same man with and without a white coat and the same woman with and without a white coat, were shown to the children and their parents, and both were asked which of each pair they would like to have as their or their child's doctor, respectively. Parents filled out a questionnaire rating the appropriateness of various aspects of a physician's attire and appearance. RESULTS: The children selected the person in the white coat 69% of the time. The parents also selected the white coat more often (66%). On the questionnaire parents identified a name tag as the most appropriate item of dress followed by a white coat. A groomed mustache and groomed beard were also rated favorably. Open-toed sandals, clogs, and shorts were rated negatively, while parents were neutral with respect to hospital greens, blouse and skirt or dress, and shirt and tie. CONCLUSIONS: Physicians may wear a white coat without fear that they are negatively affecting their relationship with their pediatric patients four to eight years of age. The appropriateness of wearing a name tag is confirmed.

Adult↗

Application of the ribonuclease P (RNase P) RNA gene sequence for phylogenetic analysis of the genus Saccharomonospora.

Sequences of the RNase P RNA gene were investigated for the phylogenetic analysis of the genus Saccharomonospora. Aligned nucleotide sequences, determined from the PCR-amplified RNase P RNA gene of representative strains of the genus Saccharomonospora, displayed 94.2 +/- 1.3% interspecific variances. The intraspecific similarity value was 99.7-100% in all species tested. Saccharomonospora azurea K161T and 'Saccharomonospora caesia' K76T displayed identical RNase P RNA gene sequences in the region that was determined and Saccharomonospora sp. K180 showed sequences distinct from validly described species with a similarity value of 94.6 +/- 1.0%. The phylogenetic trees constructed by aligning the sequences either within the genus Saccharomonospora or with other Gram-positive bacteria were similar to the ones derived using sequences of the 16S rDNA gene. Advantageous features of this gene for application as a molecular phyletic marker are discussed.

Actinomycetales↗

The association between chronic illness and functional change among participants in a comprehensive geriatric assessment program.

OBJECTIVE: To examine the association between chronic illness and functional status change during a 3-year period in older people enrolled in an in-home comprehensive geriatric assessment (CGA) and preventive care program. DESIGN: Secondary analysis of data from a longitudinal cohort study. SETTING: Santa Monica, California. PARTICIPANTS: Two hundred two community-dwelling older persons (mean age at baseline was 81 years, 70% were women, and 72% reported good health) randomized to the intervention group in a trial of in-home comprehensive geriatric assessment and preventive care. MEASUREMENTS: We studied 13 common chronic illnesses/conditions determined clinically from an annual comprehensive evaluation by gerontologic nurse practitioners (GNPs) in consultation with study geriatricians. These target conditions included hypertension, osteoarthritis, coronary artery disease, obesity, undernutrition, urinary incontinence, sleep disorders, falls, gait/balance disorders, hearing and vision deficits, depression, and unsafe home environment. The dependent variable was functional change as measured by instrumental activities of daily living (IADL) and basic activities of daily living (BADL) assessed at baseline and annually for 3 years by independent research personnel. Potential confounding variables, including comorbid conditions and other subject characteristics, were controlled for in the analyses. RESULTS: Although functional status was similar at baseline, the presence of certain target conditions in this sample was associated significantly with functional decline in IADL and BADL during the 3-year period. Four conditions (gait/balance disorders, depression, unsafe home environment, and coronary artery disease) were associated with significant declines in IADL, and four conditions (gait/balance disorders, depression, hypertension, and urinary incontinence) were associated with significant declines in BADL. Conversely, subjects with obesity had no significant change in IADL or BADL throughout the study period and had less decline in IADL compared with nonobese subjects. CONCLUSIONS: Certain chronic conditions, particularly gait/balance disorders and depression, are associated with significant decline in functional status in older persons who receive CGA. These findings may help identify older persons at risk for greatest functional decline despite participation in CGA and may also suggest the need for more effective intervention strategies in these individuals.

Activities of Daily Living↗

Construction and characterization of a temperature-sensitive human immunodeficiency virus type 1 reverse transcriptase mutant.

A temperature-sensitive (ts) human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutant was generated by charged-cluster-to-alanine mutagenesis. The mutant virus, containing three charged residues within the RT finger domain changed to alanine (K64A, K66A, and D67A), replicated normally at 34.5 but not 39.5 degrees C. Quantitating virus particle production by p24 antigen capture or virion-associated RT activity and virus infectivity by the MAGI cell assay, we found that (i) mutant virions produced at the permissive temperature were indistinguishable from wild-type virus in assays performed at the nonpermissive temperature, suggesting that the ts mutation did not impair early steps in the virus replication cycle and that the mutant RT enzyme was not ts; and (ii) virus particle production in cells transfected with the ts mutant at the nonpermissive temperature was comparable to that of wild-type virus. However, the particle-associated RT activity and infectivity of mutant virions produced at the nonpermissive temperature were greatly reduced when assays were conducted at the permissive temperature. These results are consistent with an irreversible ts event affecting RT that occurs during virus particle production. Radioimmunoprecipitation analyses revealed that both p66 and p51 RT subunits were absent from mutant virions generated at 39.5 degrees C. The presence of normal levels of HIV-1 integrase in mutant particles produced at the nonpermissive temperature was inconsistent with defective Gag-Pol synthesis or Gag-Pol incorporation into progeny virions. Furthermore, wild-type levels of the mutant Pr160(gag-pol) were detected in virions produced at the nonpermissive temperature when the HIV-1 protease was inactivated by site-specific mutagenesis. Taken together, these results are most consistent with a ts defect affecting the degradation or aberrant processing of the mutated RT during its processing/maturation within nascent particles.

Alanine↗