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

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: 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

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

PURPOSE: To establish the role of stereotactic radiosurgery (SRS) for the treatment of patients with angiographically occult vascular malformation (AOVM). MATERIALS AND METHODS: Eleven patients (12 lesions) with AOVM were treated with linear accelerator-based SRS between February 1995 and December 1999. A magnetic resonance imaging of each patients showed well-circumscribed vascular lesion with reticulated core of heterogeneous signal intensity and peripheral rim of low signal intensity. SRS were performed with the median peripheral dose of 16 Gy (range 13~25). A single isocenter was used with median collimator size of 14 mm (range 8~20) diameter. RESULTS: With a median follow-up period of 42 months (range 12~56), rebleeding occurred in 3 AOVMs at 5, 6 and 12 months after SRS but no further bleeding did. Two patients experienced radiation-induced necrosis associated with permanent neurologic deficit and one patient showed transient edema of increased T2 signal intensity. CONCLUSION: SRS may be effective for the prevention of rebleeding in AOVM located in surgically inaccessible region of the brain. Careful consideration should be needed in the decision of case selection and dose prescription because the incidence of radiation-induced complications is too high to be accepted.
Brain ; Edema ; Follow-Up Studies ; Hemorrhage ; Humans ; Incidence ; Magnetic Resonance Imaging ; Necrosis ; Neurologic Manifestations ; Prescriptions ; Radiosurgery* ; Vascular Malformations*

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

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

PURPOSE: To evaluate the role of LINAC-based stereotactic radiosurgery (SRS) in the management of meningiomas, we reviewed clinical response, image response, neurological deficits for patients treated at our institution. METHODS AND MATERIALS: Between February 1995 and December 1999, twenty-six patients were treated with SRS. Seven patients had undergone prior resection. Nineteen patients received SRS as the initial treatment. There were 7 male and 19 female patients. The median age was 51 years (range, 14~67 years). At least one clinical symptom presented at the time of SRS in 17 patients and cranial neuropathy was seen in 7 patients. The median tumor volume was 4.7 cm3 (range, 0.7~16.5 cm3). The mean marginal dose was 15 Gy (range, 10~20 Gy), delivered to the 80% isodose surface (range, 46~90%). The median clinical and imaging follow-up periods were 27 months (range, 1-71 months) and 25 months (range, 1~52 months), respectively. RESULTS: Of 14 patients who had clinical follow-up of one year or longer, thirteen patients (93%) were improved clinically at follow-up examination. Clinical symptom worsened in one patient at 4 months after SRS as a result of intratumoral edema, who underwent surgical resection at 7 months. Of 14 patients who had radiologic follow-up of one year or longer, tumor volume decreased in 7 patients (50%) at a median of 11 months (range, 6~25 months), remained stable in 6 patients (43%), and increased in one patient (7%), who underwent surgical resection at 44 months. New radiation-induced neurological deficits developed in six patients (23%). Five patients (19%) had transient neurological deficits, completely resolved by conservative treatment including steroid therapy. Radiation-induced brain necrosis developed in one patient (3.8%) at 9 months after SRS who followed by surgical resection of tumor and necrotic tissue. CONCLUSIONS: LINAC-based SRS proves to be an effective and safe management strategy for small to moderate sized meningiomas, inoperable, residual, and recurrent, but long-term follow-up will be necessary to fully evaluate its efficacy. To reduce the radiation-induced neurological deficit for large size meningioma and/or in the proximity of critical and neural structure, more delicate treatment planning and optimal decision of radiation dose will be necessary.
Brain ; Cranial Nerve Diseases ; Edema ; Female ; Follow-Up Studies ; Humans ; Male ; Meningioma* ; Necrosis ; Particle Accelerators ; Radiosurgery* ; Tumor Burden