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Biomedical subjects

C Ahn

Publications and source records attributed to C Ahn.

At least 163 records · Page 9Linked to original sources
PubMed1996

[Immunohistochemical detection of bcl-2 and MIB-1/Ki-67 in breast cancer: retrospective analysis of 238 cases].

We considered of interest to determine the possible interrelationship between the proliferation-related marker MIB-1/Ki-67 and the bcl-2, a protein involved in the blockage of apoptosis, and whether they contributed to the prognosis of breast cancer. For this purpose we carried out a retrospective immunohistochemical study of 238 cases of stage I and II breast carcinomas with a follow up of at least 5 years. The study revealed that high expression of MIB-1 was associated with high nuclear and histological grades (p < 0.001 for both), negative estrogen receptor status (p = 0.009) and progesterone status (p = 0.004), and younger age (p = 0.014). High bcl-2 expression was associated with smaller tumor size (p = 0.001), positive estrogen and progesterone receptors (p < 0.001 for both); low nuclear grade (p < 0.001), low histological grade (p < 0.002), stage I disease (p = 0.01) and low MIB-1 expression (p = 0.025). The univariate Cox regression showed a significant association of high MIB-1 expression (p = 0.002) and low bcl-2 expression (p = 0.04) with shorter OS. Furthermore, MIB-1 expression was a significant independent predictor of OS (p = 0.002) as showed by stepwise Cox regression analysis.

Antibodies, Monoclonal↗
PubMed1995

Utilization of the leucocin A export system in Leuconostoc gelidum for production of a Lactobacillus bacteriocin.

The lactacin F complex, composed of LafA and LafX peptides, is produced by Lactobacillus johnsonii VPI 11088 (ATCC 11506) and is active against various lactobacilli and Enterococcus faecalis. The genetic determinants encoding the lactacin F peptides, LafA and LafX, are organized in a chromosomal operon comprised of genes lafA, lafX, and ORFZ. The lactacin F operon was introduced into Leuconostoc (Lc.) gelidum UAL187-22 which produces leucocin A. Leucocin A, a plasmid-encoded bacteriocin, inhibits E. faecalis, Listeria monocytogenes, and other lactic acid bacteria. The culture supernatant of the Leuconostoc transformant containing the lactacin F operon inhibited both lactacin F-and leucocin A-sensitive indicators. Concurrent expression of both bacteriocins did not alter the production of native leucocin A. Additive inhibitory effects due to the presence of both bacteriocins were not observed. An isogenic derivative of UAL187-22, which has lost the leucocin-encoding plasmid, was unable to produce active lactacin F when transformed with the appropriate recombinant plasmid. The ability of Lc. gelidum UAL187-22 to produce lactacin F demonstrates that the export system for leucocin A is capable of producing both bacteriocins simultaneously.

Amino Acid Sequence↗
PubMed1995

Estimation of a common odds ratio under binary cluster sampling.

We present results from a simulation study for the estimation of a common odds ratio in multiple 2 x 2 tables when the data are correlated within clusters. We model the correlation of the data by the beta-binomial distribution. Through a simulation study, we compare the Mantel-Haenszel estimator with Rao and Scott's estimator in terms of their biases, observed variances, relative efficiencies of their variances and 95 per cent coverage proportions. We limit the simulation study to the case where there are the same number of subjects in each cluster and the same number of observations in each row of each stratum. When rho = 0, we recommend use of the Mantel-Haenszel estimator gamma MH with an unadjusted variance and Rao and Scott's estimator gamma RSP with a pooled design effect. In general, when rho > 0, we recommend the Mantel-Haenszel estimator gamma MH with an adjusted variance and Rao and Scott's estimator gamma RSP with a pooled design effect.

Bias↗
PubMed1995

Phase I study of mitomycin C and menadione in advanced solid tumors.

A phase I study of mitomycin C with menadione (2-methyl-1,4-naphthoquinone, a vitamin K analogue which lowers intracellular pools of reduced glutathione) was designed as an approach to overcoming tumor cell resistance to alkylating agent chemotherapy. Patients with refractory solid tumors (n = 51) were treated with a 48-h continuous intravenous infusion of menadione followed by a bolus intravenous dose of mitomycin C at the completion of the menadione infusion. Initial menadione doses of 8.0 and 4.0 g/m2 over 48 h were associated with hemolysis, so subsequent dose levels of menadione ranged from 1.0 to 3.0 g/m2 with mitomycin C from 5 to 20 mg/m2. All three patients treated with menadione at 8.0 g/m2 and the single patient treated at 4.0 g/m2 with mitomycin C at 5 mg/m2 developed clinically significant hemolysis despite the presence of red blood cell glucose-6-phosphate dehydrogenase. Subsequently, a revised escalation scheme for menadione was used, and all patients tolerated menadione doses of 1-2.5 g/m2 over 48 h with mitomycin C doses up to 20 mg/m2. Since the 3.0 g/m2 dose of menadione was associated with mild hemolysis in three of four patients, the maximum tolerated dose of menadione was established at 2.5 g/m2. All of the mitomycin dose levels were tolerated without unexpected toxicities attributable to the combination. Prolonged infusions of menadione at doses which have been associated with lowering of intracellular glutathione pools in short-term exposure are limited by dose-dependent hemolysis, probably due to depletion of erythrocyte glutathione by menadione-related redox cycling. There was no detectable deleterious effect of pre-exposure to menadione on mitomycin C tolerance. We recommend a combination of menadione at 2.5 g/m2 as a continuous intravenous infusion and mitomycin C at 15 mg/m2 for further study in solid tumors, for which treatment with single-agent mitomycin C is appropriate.

Adult↗
PubMed1995

Mitomycin C and menadione for the treatment of lung cancer: a phase II trial.

A phase II trial of menadione [2.5 gm/m2 as a continuous intravenous (i.v.) infusion over 48 hours] followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4 to 6 weeks was performed in 23 patients with advanced lung cancer. Menadione, a vitamin K analog which lowers intracellular pools of reduced glutathione (GSH), was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating agent chemotherapy. The median age of patients entered on this trial was 62 years; performance status ranged from 60-90%. Two of the 23 patients (9%; 95% confidence interval, 1% to 28%) had objective responses lasting 3.5 months and 13 months respectively, while 4 additional patients developed short unconfirmed responses (lacking follow-up response data to estimate response duration). Median survival for all patients was 5.5 months. Treatment with mitomycin C and menadione was well tolerated except for hematologic toxicity and cardiac events of unclear relationship to the study drugs. Thirty-one percent of treatment courses were complicated by grade 3 or 4 hematologic toxicity including one episode of hemolytic anemia. One patient developed interstitial pneumonitis. Two patients developed a decrease in left ventricular ejection fraction: one patient remained asymptomatic, but the other patient developed congestive heart failure. Although only 9% of patients had confirmed objective responses, 28% (5 of 18) of the patients with non-small cell lung cancer demonstrated biological activity (tumor regression fulfilling the criteria for objective response on a single occasion but 3 patients lacking a follow-up measurement to document response duration) to this combination of mitomycin C and menadione. We conclude that further studies of chemomodulation in non-small cell lung cancer are appropriate.

Adult↗
PubMed1995

Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial.

A phase II trial of menadione (2.5 g/m2 as a continuous intravenous infusion over 48 h) followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4-6 weeks was performed in 43 patients with advanced gastrointestinal cancer. Menadione, a vitamin K analog that lowers intracellular pools of reduced glutathione, was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating-agent chemotherapy. The median age of patients entered on this trial was 58 years; performance status ranged from 60%-100%. None of the 43 evaluable patients obtained an objective response to this combination regimen. Median survival was 6.6 months. Treatment with menadione and mitomycin C was reasonably well tolerated except for hematological toxicity. A total of 27% of treatment courses were complicated by grade 3 or 4 hematological toxicity including one episode of hemolytic anemia and one episode of hemolytic uremic syndrome. One patient developed irreversible interstitial pneumonitis, and 1 patient had an asymptomatic decrease in the left-ventricular ejection fraction. Despite preclinical evidence indicating that menadione pretreatment enhances the cytotoxicity of mitomycin C, our study documents the resistance of advanced gastrointestinal cancers, particularly colorectal cancer, to mitomycin C modulated by menadione.

Adult↗
PubMed1995

Expression of type 1 plasminogen activator inhibitor in renal tissue in murine lupus nephritis.

Many renal diseases are associated with fibrin deposition in the glomeruli, a situation that reflects an abnormality in the balance between the coagulation and fibrinolytic systems. We recently demonstrated that normal mouse kidney contains very low levels of type 1 plasminogen activator inhibitor (PAI-1), a potent anti-fibrinolytic protein, but that during endotoxemia, large amounts of PAI-1 protein and mRNA are expressed in glomerular and peritubular endothelial cells. These results raise the possibility that overexpression of PAI-1 in the glomerulus may contribute to the ongoing pathology seen in renal disease. To directly investigate this possibility, we studied PAI-1 expression in MRL/lpr mice, using in situ hybridization and immunohistochemistry. Female MRL/lpr mice develop early onset lupus glomerulonephritis (GN), a disease in which fibrin deposition is detected in the glomerulus and in which anti-coagulation therapy improves the prognosis. We detected very low levels of PAI-1 mRNA and antigen in the smooth muscle cells of renal vessels and in the renal papilla of 16 control mice. In contrast, PAI-1 was expressed in relatively high levels throughout the kidneys of 33 out of 34 diseased mice, both within the glomerulus and also in tubules and vessels. Moreover, the level of PAI-1 in the tissues seemed to correlate with the severity of the disease. PAI-1 expression was localized to endothelial cells, parietal epithelial cells, tubular epithelial cells and infiltrating mononuclear cells in the tubulointerstitium. None of these cells express detectable levels of PAI-1 in the normal kidney. The inappropriate expression of PAI-1 in the kidneys of mice with lupus GN suggests that this important inhibitor of fibrinolysis may play a role in the pathogenesis of this disease process.

Animals↗
PubMed1995

Association of silent myocardial ischemia with new atherothrombotic brain infarction in older patients with extracranial internal or common carotid arterial disease with and without previous atherothrombotic brain infarction.

OBJECTIVE: To correlate silent myocardial ischemia with the incidence of new atherothrombotic brain infarction (ABI) in older patients with 40 to 100% extracranial carotid arterial disease (ECAD) with and without prior ABI. DESIGN: In a prospective study of 208 older patients with 40 to 100% ECAD diagnosed by carotid duplex ultrasonography, 24-hour ambulatory electrocardiograms were obtained to detect silent myocardial ischemia. At 42-month mean follow-up, silent myocardial ischemia was correlated with the incidence of new ABI in patients with and without prior ABI. SETTING: A large long-term health care facility where 208 older patients with 40 to 100% ECAD and technically adequate 24-hour ambulatory electrocardiograms for detecting silent myocardial ischemia were studied. PATIENTS: The 208 patients included 68 men and 140 women, mean age 81 +/- 8 years (range 60 to 100). One-hundred three (50%) of the patients had prior ABI. MEASUREMENTS AND MAIN RESULTS: Sixty-nine (33%) of the 208 patients had silent myocardial ischemia. Mean follow-up was 42 +/- 25 months (range 3 to 101 months). At follow-up, the incidence of new ABI was 64% in patients with prior ABI and 32% in patients with no prior ABI (P < .0001). At follow-up, the incidence of new ABI was 65% in patients with silent ischemia and 40% in patients with no silent ischemia (P = .0005). The multivariate Cox regression model showed that patients with prior ABI have a 2.5 times higher chance of developing new ABI than those without prior ABI after controlling other prognostic variables. Patients with silent ischemia have a 2.1 times higher probability of developing new ABI than those without silent ischemia after controlling other prognostic variables. CONCLUSIONS: Prior ABI and silent ischemia are independent risk factors for the development of new ABI in patients with 40 to 100% ECAD. This probably reflects that silent ischemia is a marker for more advanced or more significant atherosclerotic disease rather than a causal factor for ABI.

Aged↗
PubMed1995

Modeling the glottal volume-velocity waveform for three voice types.

The purpose of this study was to model features of the glottal volume-velocity waveform for three voice types: modal voice, vocal fry, and breathy voice. The study analyzed data measured from two sustained vowels and one sentence uttered by nine adult, male subjects who represented examples of the three voice types. The primary analysis procedure was glottal inverse filtering, which estimated the glottal volume-velocity waveform. The estimated glottal volume-velocity waveform was then fit to an LF model waveform. Four parameters of the LF model were adjusted to minimize the mean-squared error between the estimated glottal waveform and the LF model waveform. Statistical averages and standard deviations of the four parameters of the LF glottal waveform model were calculated using the data for each voice type. The four LF model parameters characterize important low-frequency features of the glottal waveform, namely, the glottal pulse width, pulse skewness, abruptness of closure of the glottal pulse, and the spectral tilt of the glottal pulse. Statistical analysis included ANOVA and multiple linear regression analysis. The ANOVA results demonstrated that there was a difference in three of the four LF model parameters for the three voice types. The linear regression analysis between the four LF model parameters and a formal rating by a listening test of the quality of the three voice types was used to determine the most significant LF model parameters for each voice type. A simple rule was devised for synthesizing the three voice types with a formant synthesizer using the LF glottal waveform model. Listener evaluations of the synthesized speech tended to confirm the results determined by the analysis procedures.

Algorithms↗
PubMed1995

Hemorrhagic fever with renal syndrome caused by the Seoul virus.

The Seoul virus is an important etiologic agent in hemorrhagic fever with renal syndrome (HFRS), and infections with the Seoul virus are less severe than those with the Hantaan virus. However, the information on HFRS caused by the Seoul virus is limited in Korea. Retrospective clinical analysis was done on 30 patients with Seoul virus infection who had been diagnosed as having HFRS by clinical features and serologic testing by the plaque reduction neutralization test from 1986 to 1991 at the Seoul National University Hospital. They were compared with 69 patients with Hantaan virus infection. The Seoul virus was the etiologic agent in 25% of Korean HFRS and the major cause of HFRS during the summer season although infections occurred throughout the year. The Seoul virus infection had a milder degree of bleeding and renal derangement but had severer liver dysfunction than the Hantaan virus infection. Renal histopathologic findings revealed a milder degree of hemorrhage and vascular changes than cases involving Hantaan virus infection. The precise mechanisms of vascular dysfunction and organ involvement in Seoul virus infection, however, still remain to be explored.

Adult↗
PubMed1995

Phase I trial of carboplatin and infusional cyclosporin in advanced malignancy.

PURPOSE: To determine the maximal-tolerated dose (MTD) of infusional cyclosporine (CSA) with fixed-dose carboplatin (CBDCA). PATIENTS AND METHODS: Clonogenic cytotoxicity assays were performed to assess the effect of CSA on reversal of resistance to CBDCA. The phase I study was performed in three phases. In phases 1 and 2, escalating-dose CSA (5, 7.5, 8.8, or 9.5 mg/kg/d) with fixed-dose CBDCA 300 or 250 mg/m2 were administered. Phase 3 required an initial cycle of CBDCA 250 mg/m2 alone, followed by combination therapy with CBDCA 250 mg/m2 and CSA (8.8, 9.5, or 10.0 mg/kg/d). RESULTS: Preincubation of platinum-resistant A2780 human ovarian cancer cells with CSA 2 micrograms/mL significantly enhanced CBDCA cytotoxicity in clonogenic assays. Fifty-one patients received 130 courses of therapy. The phase 1 MTD was thrombocytopenia (CSA 7.5 mg/kg/d and CBDCA 300 mg/m2) attributable to the effects of CBDCA alone. The phase 2 MTD was reversible nephrotoxicity (serum creatinine elevations to 3.6 and 4.4 mg/dL) and neutropenia (CSA 9.5 mg/kg/d and CBDCA 250 mg/m2). In phase 3, headache was observed in five patients and hypertension in one patient at CSA 10 mg/kg/d. The expected change in platelet count predicted for CBDCA alone was compared with the actual change; no excessive thrombocytopenia was observed with addition of CSA. Steady-state CSA levels of 2 micrograms/mL capable of reversing platinum resistance in vitro were observed. Four objective responses were observed. CONCLUSION: CSA is effective in reversing CBDCA resistance in A2780 ovarian cancer cells. Short-term infusions of CSA < or = 8.8 mg/kg/d in combination with CBDCA are well-tolerated for heavily pretreated patients and result in CSA levels known to reverse CBDCA resistance in vitro.

Adult↗
PubMed1995

Intestinal parasitic infections in the residents of an emigration camp in Tijuana, Mexico.

We examined stool specimens of the residents in the emigration camp in Tijuana, Mexico for helminth eggs or protozoan cysts with formalin-ethyl acetate concentration method in February and July 1992. Out of 92 examined samples, number of positive was 49 (53.3%). While number of cumulative positive was 66 (71.7%). Cysts of Entamoeba coli (29.3%) Giardia lamblia (9.8%), Entamoeba histolytica (7.6%), and eggs of Taenia spp. (6.5) were most frequently observed. Filtered water supply and chemotherapy were required in this camp.

Adolescent↗
PubMed1995

One-stage primary repair of distal esophageal perforation using fundic wrap.

Esophageal leak following primary repair of esophageal perforation is a serious complication that can lead to severe mediastinitis and sepsis. Complete diversion with esophageal exclusion or resection is designed to minimize further mediastinal contamination. However, this approach is not necessarily associated with less morbidity or mortality. Furthermore, a second stage operation is required to restore esophageal continuity. From 1986 to 1994, we performed a one-stage primary repair of the distal esophagus in seven patients with either iatrogenic (n = 5) or spontaneous (n = 2) perforations and reinforced the repair by a fundic wrap. One patient underwent an additional modified Heller myotomy for achalasia. Delay between perforation and operation was less than 6 hours in 3 patients, 6 to 24 hours in 2 patients, and greater than 24 hours in 2 patients. Only one patient (14%) developed a small esophageal leak that spontaneously resolved with adequate mediastinal drainage, intravenous antibiotics, and aggressive nutritional support. One patient (14%), whose repair was delayed by 12 hours, died postoperatively of profound sepsis. This patient was moribund from sepsis preoperatively, and postmortem examination of the esophagus revealed no evidence of esophageal leak. Esophageal continuity was maintained in all patients. The median length of stay was 21 days (range, 15-58 days). We conclude that primary reinforced repair of esophageal perforation using a fundic wrap is an effective method of treatment for distal esophageal perforation, even when the repair is delayed by more than 24 hours.

Adult↗