p27(kip1) protein, a cyclin-dependent kinase inhibitor, has been reported to be a powerful negative prognostic marker in patients with breast carcinoma. However, to this day, studies on p27(kip1) protein expression in ductal carcinoma in situ (DCIS) have been extremely limited. We studied the immunohistochemical expression of p27(kip1) protein in 49 cases of the DCIS and compared the findings to the clinicopathologic parameters, cyclin D1, p53 and estrogen receptor (ER). Positive nuclear staining of p27(kip1) protein was identified in 23 (46.9%) cases. The p27(kip1) protein expression correlated positively with the cyclin D1 immunopositivity (p<0.005) and ER expression (p<0.005). No significant associations were seen in the p27(kip1) protein expression and clinicopathologic parameters. The overexpression of cyclin D1 (59.2% of the cases) correlated positively with ER expression (p<0.001). The p53 protein expression was identified in 30.6% and seemed to be correlated inversely with ER expression (p=0.06). The DCISs with high grade nuclei were more likely to be p53-positive (p<0.05). Our data suggest that the expression of p27(kip1) protein as well as cyclin D1 and p53 protein may be influenced by the ER status in DCIS. The significantly positive correlation of p27(kip1) protein and cyclin D1 expression (p<0.005) supports the theory that the balance of the two opposing signals is important in determining the cell proliferation in breast cancers. Therefore, a comprehensive understanding of loop reaction of p27(kip1)-cyclin D1-ER may be necessary for the treatment of DCIS.
Breast Neoplasms ; Breast* ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating* ; Cell Proliferation ; Cyclin D1* ; Cyclins* ; Estrogens ; Humans ; Phosphotransferases ; Staphylococcal Protein A

Eleven hantavirus isolates were obtained by innoculation of viremic blood, urine, or autopsy tissue specimens from ten HFRS patients, and sera were obtained from five patients with HFRS. The disease was diagnosed by clinical manifestations and indirect immunofluorescent antibody technique. We obtained 6 hantaviruses from gene bank. So, we analyzed 22 hantavirus samples to elucidate the genetic diversity. The hantaviral RNAs were extracted and 365 base-pair complementary DNAs of M segment were obtained by reverse transcriptase polymerase chain reaction (RT-PCR) and 326 base-pair by nested PCR. The nucleotide sequences of amplified cDNA fragments were determined by the direct sequencing method using automatic DNA sequence analyzer. We got full M segment sequences of 28 reported hantaviruses with medline searching, and aligned them with our 22 samples, and the phylogenetic analysis for nucleotide and amino acid sequences were done by the Clustal method. The nucleotide and amino acid sequences of Hantaan virus 17 samples showed high (above 90%) homology with 76-118 strain, but 2 samples showed significant differences with 76-118 strain and with other 17 samples. The 3 Seoul virus samples showed high intraspecies differences in 1 sample, and showed singnificant differences with SR-11 strain. In phyogenetic tree analysis, Puumala virus and Hantavirus pulmonary syndrome viruses showed high homology, but Hantaan and Seoul viruses showed significant genetic diversity among strains. In conclusion, hantaviruses isolated from HFRS patients showed genetic diversity compared with those isolated from rodent hosts.
Amino Acid Sequence ; Autopsy ; Base Sequence* ; DNA, Complementary ; Genetic Variation ; Hantaan virus ; Hantavirus Pulmonary Syndrome ; Hantavirus* ; Hemorrhagic Fever with Renal Syndrome* ; Humans ; Korea* ; Polymerase Chain Reaction ; Puumala virus ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; Rodentia ; Seoul virus

Pulmonary edema is a major cause of mortality due to acute lung injury (ALI). The involvement of protein kinase C-delta (PKC-delta) in ALI has been a controversial topic. Here we investigated PKC-delta function in ALI using PKC-delta knockout (KO) mice and PKC inhibitors. Our results indicated that although the ability to produce proinflammatory mediators in response to LPS injury in PKC-delta KO mice was similar to that of control mice, they showed enhanced recruitment of neutrophils to the lung and more severe pulmonary edema. PKC-delta inhibition promoted barrier dysfunction in an endothelial cell layer in vitro, and administration of a PKC-delta-specific inhibitor significantly increased steady state vascular permeability. A neutrophil transmigration assay indicated that the PKC-delta inhibition increased neutrophil transmigration through an endothelial monolayer. This suggests that PKC-delta inhibition induces structural changes in endothelial cells, allowing extravasation of proteins and neutrophils.
Acute Lung Injury* ; Animals ; Capillary Permeability* ; Endothelial Cells ; Lung ; Mice ; Mortality ; Neutrophils ; Protein Kinase C-delta* ; Protein Kinases* ; Pulmonary Edema

BACKGROUND/AIMS: It is recommended that duodenal ulcer patients who are infected with H. pylori should be treated with eradication therapy, whether the ulcer is active or in remission. However, there has been no report on the effect of eradication treatment in patients with incidentally found S-2 stage duodenal ulcer scar. METHODS: We prospectively enrolled 80 H. pylori-positive patients with S-2 stage duodenal ulcer scar who have no past history of ulcer treatment. Treatment group received triple therapy consisted of omeprazole, amoxicillin, and clarithromycin for 2 weeks, whereas control group received no treatment. The follow-up endoscopy was performed every 1 year and when the patients have symptoms of ulcer disease. Fifty-three patients were followed up for more than 1 year. RESULTS: The eradication rate of the treatment group was 92.9%. During the follow-up period of 14.7 months, 20% (5/25) of patients in the control group (2 gastric ulcers and 3 duodenal ulcers) and 3.6% (1/28) of patients in the treatment group (1 duodenal ulcer) developed active or healing stage peptic ulcers (p=0.089). CONCLUSIONS: Our results suggest that H. pylori eradication may he effective in preventing peptic ulcers in patients with S-2 stage duodenal ulcer scar.
Amoxicillin ; Cicatrix* ; Clarithromycin ; Duodenal Ulcer* ; Endoscopy ; Follow-Up Studies ; Helicobacter pylori* ; Helicobacter* ; Humans ; Omeprazole ; Peptic Ulcer ; Prospective Studies ; Stomach Ulcer ; Ulcer

Myristoylated alanine-rich C kinase substrate (MARCKS) is a widely distributed protein kinase C (PKC) substrate and has been implicated in actin cytoskeletal rearrangement in response to extracellular stimuli. Although MARCKS was extensively examined in various cell culture systems, the physiological function of MARCKS in the central nervous system has not been clearly understood. We investigated alterations of cellular distribution and phosphorylation of MARCKS in the hippocampus following kainic acid (KA)-induced seizures. KA (25 mg/kg, i.p.) was administered to eight to nine week-old C57BL/6 mice. Behavioral seizure activity was observed for 2 h after the onset of seizures and was terminated with diazepam (8 mg/kg, i.p.). The animals were sacrificed and analyzed at various points in time after the initiation of seizure activity. Using double-labeling immunofluorescence analysis, we demonstrated that the expression and phosphorylation of MARCKS was dramatically upregulated specifically in microglial cells after KA-induced seizures, but not in other types of glial cells. PKC alpha, beta I, beta II and delta, from various PKC isoforms examined, also were markedly upregulated, specifically in microglial cells. Moreover, immunoreactivities of phosphorylated MARCKS were co-localized in the activated microglia with those of the above isoforms of PKC. Taken together, our in vivo data suggest that MARCKS is closely linked to microglial activation processes, which are important in pathological conditions, such as neuroinflammation and neurodegeneration.
Up-Regulation/drug effects ; Time Factors ; Seizures/chemically induced/*metabolism ; Protein Kinase C-delta/analysis ; Protein Kinase C-alpha/analysis ; Protein Kinase C/*analysis ; Protein Biosynthesis/drug effects ; Phosphorylation/drug effects ; Microscopy, Confocal ; Microglia/cytology/drug effects/*metabolism ; Mice, Inbred C57BL ; Mice ; Membrane Proteins/*analysis/metabolism ; Kainic Acid/*toxicity ; Isoenzymes/analysis ; Intracellular Signaling Peptides and Proteins/*analysis/metabolism ; Immunohistochemistry ; Animals

BACKGROUND/AIMS: Carcinogenesis is characterized by the abnormal regulation of cell cycle. The abnormal expression of the regulators of cell cycle may be related to the prognosis. Since the clinical significance of the expression of the three proteins in colorectal carcinomas is still controversial, we evaluated the prognostic value of the expression of cyclin E, p27 and mutant p53 in stage II colorectal cancer. METHODS: The expression levels of cyclin E, p27 and mutant p53 proteins in 41 patients with stage II colorectal carcinomas were analyzed by immunohistochemistry. RESULTS: In the univariate analysis, the level of CEA at diagnosis was associated with disease relapse. In the multivariate analysis, the clinicopathological variables such as age, gender, site of primary tumor, tumor size, state of tumor differentiation and preoperative plasma CEA level were not associated with disease relapse. When Kaplan-Meier survival curves were constructed to determine the prognosis, cyclin E, p27 and mutant p53 expressions did not predict poor prognosis. CONCLUSIONS: Our results suggested that the expression of cyclin E, p27 and mutant p53 proteins did not predict the clinical outcome in the stage II colorectal carcinomas.
Adenocarcinoma/chemistry/*diagnosis/mortality/pathology ; Adult ; Aged ; Aged, 80 and over ; Cell Cycle Proteins/*analysis ; Colorectal Neoplasms/chemistry/*diagnosis/mortality/pathology ; Cyclin E/*analysis ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Mutation ; Prognosis ; Protein p53/*analysis/genetics ; Survival Rate ; Tumor Markers, Biological/analysis ; Tumor Suppressor Proteins/*analysis

BACKGROUND/AIMS: Safety of endoscopic procedures has been a major issue over the last 10 years. Most endoscopy units use 2% glutaraldehyde and automated endoscope reprocessors (AERs) for disinfecting gastrointestinal endoscopes. We attempted an in-use evaluation of the current reprocessing procedures. METHODS: Thirty flexible endoscopes were randomly collected just after upper endoscopic examinations and were disinfected using 2% glutaraldehyde in an AER. Cultures were taken from biopsy channels (S-1), tip of the insertion tubes (S-2), umbilical cords (S-3), and angulation knobs (S-4). RESULTS: In 63.3% (19/30) of endoscopes, there was no microbial contamination after disinfection procedures. The culture positive rates of S-1, S-2, S-3, and S-4 samples were 20.0%, 0.0%, 3.3%, and 20.0%, respectively. Microorganisms of 13 species were identified, but there was no pathogen related with reported infectious complications after endoscopic procedures. CONCLUSIONS: Current disinfection procedure using 2% glutaraldehyde and an AER appears to be very effective in decontaminating patient-used endoscopes. Low level microbial contamination of endoscopes after conventional reprocessing methods may not impose great risk on patients.
Biopsy ; Disinfection* ; Endoscopes* ; Endoscopes, Gastrointestinal ; Endoscopy ; Glutaral* ; Humans ; Umbilical Cord

Bovine mastitis is an infectious disease with a major economic influence on the dairy industry worldwide. Many factors such as environment, pathogen, and host affect susceptibility or resistance of an individual cow to bovine mastitis. Recently, there has been considerable interest in defining genetic and immunological markers that could be used to select for improved disease resistance. In this study we have analyzed the lymphocyte subpopulations of mastitis-resistant and susceptible cows using monoclonal antibodies specific for bovine leukocyte differentiation antigens and flow cytometry. We have also used a microarray typing technique to define the bovine leukocyte antigen (BoLA) class I and class II haplotypes associated with resistance or susceptibility to bovine mastitis. A striking finding of the present study is that susceptibility to mastitis was associated with major histocompatibility complex (MHC) haplotypes that have only a single set of DQ genes. The study also revealed that susceptible cows had CD4:CD8 ratios of less than one in both their mammary gland secretions and peripheral blood. These results raise the possibility that the number of DQ genes that a cow has and/or a cow's CD4:CD8 ratio could be used as indicators of susceptibility to bovine mastitis.
Alleles ; Animals ; Antigens, Differentiation/immunology ; Cattle ; Cell Count/veterinary ; Female ; Flow Cytometry/veterinary ; Genetic Predisposition to Disease ; Histocompatibility Antigens/genetics/immunology ; Korea ; Leukocytes, Mononuclear/cytology/*immunology/microbiology ; Lymphocyte Subsets/*immunology/microbiology ; Mastitis, Bovine/genetics/*immunology/microbiology ; Oligonucleotide Array Sequence Analysis/veterinary ; Statistics, Nonparametric

PURPOSE: To assess the radiologic response and cranial nerve morbidity in intracranial schwannoma patients treated with stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT). MATERIALS AND METHODS: Twenty-six patients with intracranial schwannoma were treated with linear accelerator- based SRS or FSRT between February 1995 and October 1999. The origin of schwannoma was acoustic nerve in twenty-one patients, facial nerve in two, trigeminal nerve in two, and glossopharyngeal nerve in one. SRS were performed with the median peripheral dose of 14 Gy (range 12-16), and FSRT were done with the median peripheral dose of 25 2 Gy (range 50-60). RESULTS: With a median follow-up period of 33 months (range 12-67), the local control rate was 100%. Tumorregression was noted in eleven patients, and tumor stabilization was found in the remaining fifteen. Useful hearing preservation was achieved in two of three patients. Facial nerve neuropathy was shown in two patients and one patients developed trigeminal nerve neuropathy. CONCLUSION: Stereotactic radiotherapy including SRS and FSRT provided excellent local control in intracranial schwannoma. It shows the possibility of a high rate of hearing preservation and an acceptable neurotoxicity, although the number of patients are small and follow-up is relatively short.
Cochlear Nerve ; Cranial Nerves ; Facial Nerve ; Follow-Up Studies ; Glossopharyngeal Nerve ; Hearing ; Humans ; Neurilemmoma* ; Radiosurgery* ; Radiotherapy* ; Trigeminal Nerve

BACKGROUND/AIMS: The predictory factors of the response to initial steroid therapy in active Crohn's disease has been controversial in numerous literature reviews. We evaluated any predictory factor of the response to initial steroid therapy in active Crohn's disease patients. METHODS: The medical records of 32 patients with active Crohn's disease who clinically responded to oral steroid therapy were retrospectively reviewed. The steroid responsive group was defined as the one showing maintenance of response for more than one month from steroid withdrawal and the steroid dependent group as the one showing relapse or exacerbation during steroid tapering or within 30 days from steroid withdrawal. The clinical, biochemical, and pathologic factors were evaluated. RESULTS: There were 22 male and 10 female patients. The mean age was 28.9 years. The number of steroid responsive and dependent group was 22 (68.8%) and 10 (31.2%), respectively. There were no significant differences between these two groups in age, sex, time to diagnosis, perianal lesion, extent of disease, extraintestinal manifestations, presence of granuloma, presenting features, hemoglobin, ESR, and CRP, except serum albumin level. CONCLUSIONS: Serum albumin level was significantly lower in steroid dependent group than steroid responsive group, reflecting severe inflammation in steroid dependent group.
Crohn Disease* ; Diagnosis ; Female ; Granuloma ; Humans ; Inflammation ; Male ; Medical Records ; Recurrence ; Retrospective Studies ; Serum Albumin