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Biomedical subjects

C W Ahn

Publications and source records attributed to C W Ahn.

At least 19 recordsLinked to original sources
PubMed2002

(AC)(n) polymorphism of aldose reductase gene and diabetic microvascular complications in type 2 diabetes mellitus.

Recent studies suggest that the gene encoding aldose reductase, the enzyme that converts glucose to sorbitol, may confer susceptibility to microvascular disease. The aim of this study therefore, was to investigate the relationship between the aldose reductase gene and type 2 diabetic microvascular complications such as diabetic nephropathy and retinopathy. DNA from 127 Korean patients with type 2 diabetes was typed for an (AC)(n) dinucleotide repeat polymorphic marker at the 5'-end of the aldose reductase gene using polymerase chain reaction. No significant difference in the frequency of the putative risk allele Z-2 was found in patients of nephropathy and retinopathy groups compared with the uncomplicated group (32.2, 34.1 vs. 25.1%, respectively, P>0.05). Similarly, no difference was found in the frequency of the putative protective allele Z+2 among any of the study groups. In conclusion, the results of the study in Korean type 2 diabetic patients do not support the hypothesis that polymorphism at the 5' end of the aldose reductase gene contributes to the susceptibility to diabetic microvascular complications.

Aged↗
PubMed2002

Clinical characteristics, GAD antibody (GADA) and change of C-peptide in Korean young age of onset diabetic patients.

AIMS: To investigate the association of clinical and immunological markers with diabetes classification in newly diagnosed young diabetic patients at disease onset. METHODS: Eighty-two diabetic patients recruited within 1 year of onset (mean age 23.0 +/- 7.1, M:F = 46:36) were divided into three groups, namely: a low fasting C-peptide (FC) level at baseline group (the low FC group (n = 14, FC < 0.18 nmol/l)), an intermediate FC group (n = 29, 0.18 nmol/l < or = FC < 0.37 nmol/l), and a high FC group (n = 39, 0.37 nmol/l < or = FC). Patients were reclassified at follow-up (mean follow-up period 3.7 +/- 1.4 years) in the same manner as described above into low FC group (n = 31), intermediate FC group (n = 20), and high FC group (n = 31). The clinical characteristics and prevalence of GADA were compared. RESULTS: Patients in the high FC group at baseline had a higher body mass index (BMI), a higher frequency of a family history of diabetes, a higher meal-stimulated C-peptide increment, a lower frequency of ketonuria, a lower frequency of history of diabetic ketoacidosis, and a lower frequency of insulin therapy at diagnosis than those in the low and intermediate FC groups at baseline. Insulin secretory capacity, which was represented by fasting C-peptide, was affected by BMI at diagnosis and the presence of GADA. All the patients of the low FC group on follow-up were finally classified as having Type 1 diabetes; moreover, the factors that determined the type of diabetes were lower BMI at onset, GADA positivity, insulin therapy, lower fasting C-peptide level and lower meal-stimulated C-peptide increment at initial admission. CONCLUSIONS: Our study suggests that follow-up involving C-peptide and GADA measurements in combination with clinical characteristics is useful for discriminating between the types of diabetes in these groups.

Adolescent↗
PubMed2001

beta-Cell dysfunction rather than insulin resistance is the main contributing factor for the development of postrenal transplantation diabetes mellitus.

BACKGROUND: Our study was undertaken to investigate the pathogenesis and possible risk factors for postrenal transplantation diabetes mellitus (PTDM). METHODS: We recruited 114 patients with normal glucose tolerance (NGT) and performed both 75-g oral glucose tolerance tests (OGTT) and short insulin tolerance tests 1 week before and 9-12 months after transplantation. RESULTS: The subjects were classified into three groups by World Health Organization criteria on the basis of OGTT after transplantation: (a) 36 (31.6%) subjects with normal glucose tolerance; (b) 51 (45.7%) subjects with impaired glucose tolerance (IGT); and (c) 27 (23.7%) subjects with postrenal transplantation diabetes mellitus. Dosages of steroid and cyclosporine were equivalent among the three groups. Before transplantation, the fasting and 2-hr plasma glucose and proinsulin/insulin (PI/I) ratios were significantly higher in the IGT and PTDM groups than in the NGT group, but the insulin sensitivity index (ISI) was not significantly different among the three groups. In addition, the area under the curve-insulin on OGTT was significantly lower in the PTDM group than in the NGT group. After transplantation, however, the ISI was increased in all groups. Furthermore, the ISI and PI/I ratios revealed significantly higher values in the PTDM group than in the NGT group after transplantation. CONCLUSIONS: These results revealed that fasting and 2-hr plasma glucose levels, as well as the proinsulin/insulin ratio before transplantation, are both possible indicators of beta-cell dysfunction and may be predictors for the development of PTDM. Furthermore, beta-cell dysfunction, rather than insulin resistance, was proven to be the main factor for the pathogenesis of PTDM.

Adult↗
PubMed2001

Mutation in hepatocyte nuclear factor-1alpha is not a common cause of MODY and early-onset type 2 diabetes in Korea.

Maturity-onset diabetes of the young (MODY)-3 with a mutation in hepatocyte nuclear factor (HNF)-1alpha has been identified in most races, but the prevalence of Korean MODY and early-onset type 2 diabetes with a mutation in this gene is unknown. To determine the prevalence of MODY and early-onset type 2 diabetes with the mutation of HNF-1alpha gene in Korea, we analyzed this gene in 69 Korean early-onset type 2 diabetics and in 35 healthy persons using the single-strand conformation polymorphism (SSCP) technique and direct sequencing. We identified one mutation in exon 4 (C900A) in only one of the 69 Korean subjects with early-onset type 2 diabetes; this mutation was silent and did not change the amino acid (Pro300). Additionally, we identified four polymorphisms: S487N, AAC-->AGC, intron 2 (nt -23), intron 7: (nt +7) and intron 9 (nt -24). However, there was no significant difference in frequencies of the four polymorphisms between the type 2 diabetes and control groups. Among type 2 diabetics, codon 487 variant showed no relationship to age at onset, body mass index, fasting blood glucose, HbA1c, lipid profile, basal C-peptide and 2 hour C-peptide. We concluded that this genetic mutation in HNF-1alpha gene may not be a common contributor to MODY and early-onset type 2 diabetes susceptibility in Korea.

Adult↗
PubMed2001

Polycystic ovarian syndrome (PCOS) and insulin resistance.

OBJECTIVES: Polycystic ovary syndrome (PCOS) presents a high risk of developing type 2 diabetes mellitus. We studied a group of women with PCOS and evaluated this defect in insulin action. METHODS: The study population consisted of nine PCOS women, six obese type 2 diabetic patients, and five controls whose body mass index (BMI) was similar to that of the nine PCOS women. The 75-g oral glucose tolerance test (OGTT) and the hyperinsulinemic euglycemic glucose clamp test were performed. Clinical characteristics and the metabolic profiles, including the insulin sensitivity index (ISI), were compared. RESULTS: PCOS women showed significantly elevated insulin responses during OGTT, but their blood glucose levels were comparable with the controls. The subjects with PCOS had more insulin resistance than the other groups. There was no difference among the groups in terms of clinical characteristics and metabolic profiles, except age, luteinzing hormone (LH), testosterone, and sex hormone binding globulin (SHBG). CONCLUSION: We conclude that PCOS women have significant insulin resistance which is independent of adiposity.

Adult↗
PubMed2001

Decrease in carotid intima media thickness after 1 year of cilostazol treatment in patients with type 2 diabetes mellitus.

A multicenter exploratory study at three university hospitals was performed to evaluate the effect of oral cilostazol on intima media thickness (IMT) in diabetic patients. A total of 141 patients was recruited in this study and randomized into a cilostazol group and a placebo (control) group. One hundred and twenty patients completed the study (i.e. 60 on cilostazol and 60 on placebo). Biochemical profiles and the IMT of the common carotid artery (CCA) determined by high-resolution B-mode ultrasonography were measured at 0, 6, and 12 months after the oral administration of 100--200 mg of cilostazol or placebo (i.e. two or four times daily for 12 months). Clinical and biochemical characteristics, the treatment modality, and microvascular diabetic complications after randomization were not significantly different between the two groups after the study. In the cilostazol treatment group, left CCA average IMT significantly decreased from 0.94+/-0.03 to 0.91+/-0.02 mm at 6 months (P<0.05), and thereafter increased to 0.92+/-0.01 mm (P>0.05) at 12 months, whereas in the control group, it increased from 0.92+/-0.03 to 0.93+/-0.01 mm at 6 months (P>0.05), and to 0.94+/-0.01 mm at 12 months (P>0.05). As for the right CCA average IMT, it decreased from 0.83+/-0.03 to 0.82+/-0.01 mm at 6 months (P<0.05), and to 0.81+/-0.01 mm at 12 months (P<0.05) in the cilostazol group, whereas it increased from 0.87+/-0.03 to 0.89+/-0.01 mm at 6 months (P<0.05), and to 0.90+/-0.01 mm at 12 months (P<0.05) in the control group (P<0.05). After correction for risk factors such as blood pressure, smoking, and lipid profiles, there were significant changes in left and right CCA average IMT for both groups (P<0.05). Left and right CCA average IMT was significantly different between the two groups (P<0.05). After making statistical corrections for blood pressure, smoking, and lipid profiles, the differences between these two groups remained significant (P<0.05). Meanwhile, there were no differences between the groups in the change of risk factors such as BMI, blood pressure, blood sugar, HbA(1c), and lipid profiles. Generally, cilostazol was well tolerated and the most common side effect in the cilostazol group was headache (12/60), mostly early in the treatment regimen. The results suggest that oral cilostazol may be helpful in the treatment of atherosclerosis in type 2 diabetic patients, although conventional cardiovascular risk factors remained unmodified.

Blood Glucose↗
PubMed2001

His-His-Leu, an angiotensin I converting enzyme inhibitory peptide derived from Korean soybean paste, exerts antihypertensive activity in vivo.

It has been reported that soybean peptide fractions isolated from Korean fermented soybean paste exert angiotensin I converting enzyme (ACE) inhibitory activity in vitro. In this study, further purification and identification of the most active fraction inhibiting ACE activity were performed, and its antihypertensive activity in vivo was confirmed. Subsequently, a novel ACE inhibitory peptide was isolated by preparative HPLC. The amino acid sequence of the isolated peptide was identified as His-His-Leu (HHL) by Edman degradation. The IC(50) value of the HHL for ACE activity was 2.2 microg/mL in vitro. Moreover, the synthetic tripeptide HHL (spHHL) resulted in a significant decrease of ACE activity in the aorta and led to lowered systolic blood pressure (SBP) in spontaneously hypertensive (SH) rats compared to control. Triple injections of spHHL, 5 mg/kg of body weight/injection resulted in a significant decrease of SBP by 61 mmHg (p < 0.01) after the third injection. These results demonstrated that the ACE inhibitory peptide HHL derived from Korean fermented soybean paste exerted antihypertensive activity in vivo.

Amino Acid Sequence↗
PubMed2000

Chronic alcohol intake differently influences glucose metabolism according to nutritional status.

We investigated the potential different effects of a chronic alcohol intake on glucose metabolism according to nutritional status in growing rats. Eighty weanling 4-week-old male Sprague Dawley rats were fed with low (5%, wt/wt) or control (22%) protein diet for 8 weeks. Each group was subdivided into alcohol (5 g/kg(-1) x day(-1)) or saline gavage rats during the last 4 weeks. At 12 weeks of age, we measured the weights of the body, pancreas, and epididymal fat; glycogen synthase activity of gastrocnemius muscle; and insulin content of the pancreas. We performed an ip glucose tolerance test and a euglycemic hyperinsulinemic clamp test. Weight gain was almost arrested in protein-deficient rats. The relative weight and insulin content of the pancreas and glycogen synthase activity were not different among the four groups, but the relative amount of epididymal fat decreased only in protein-deficient saline rats. Insulin response after glucose challenge and glucose disposal rate during the euglycemic clamp were both markedly decreased in protein-deficient saline rats, but not changed in protein-deficient alcohol rats. Protein-deficiency per se causes deterioration both in insulin secretory function and in sensitivity, but these defects are protected by a chronic alcohol intake. In a protein-sufficient state, alcohol intake gives no additional effects on glucose metabolism. Therefore, according to individual nutritional status, the metabolic effect of alcohol intake appears differently.

Adipose Tissue↗
PubMed1999

The validity of random urine specimen albumin measurement as a screening test for diabetic nephropathy.

To assess the validity of urine albumin concentration (UAC) and the urine albumin:creatine ratio (UACR) in a random urine specimen (RUS) for screening diabetic nephropathy in Korea, a total of 105 ambulatory diabetes mellitus patients (male:female, 52:53), ages 40-75 years (median 59 years) collected 105 RUSs after completing a timed 24 hour urine collection. Albumin was measured by immunonephelometry. According to the timed urinary albumin excretion rate (UAER) measured in the 24 hour collection (criterion standard), samples were classified normoalbuminuric (UAER < 20 micrograms/min; n = 50), microalbuminuric (UAER 20-200 micrograms/min; n = 30), and macroalbuminuric (UAER > 200 micrograms/min; n = 25). The receiver operating characteristics (ROC) curve of UAC and UACR in a RUS for screening of microalbuminuria (normo- and microalbuminuric samples; n = 80) and macroalbuminuria (micro- and macroalbuminuric samples; n = 55) were plotted. Pearson's coefficients of correlation of 24 hour UAER vs. UAC and UACR were 0.81 and 0.75, respectively (P < 0.001). The point of intersection with a 100%-to-100% diagonal for microalbuminuria were as follows: 31.0 mg/l for UAC and 32.5 mg/g for UACR; for macroalbuminuria 181 mg/l for UAC and 287.3 mg/g for UACR. The sensitivity and specificity of the cut-off points for microalbuminuria were 77% and 82% for UAC and 77% and 92% for UACR. The sensitivity and specificity of the cut-off points for macroalbuminuria were 84% and 90% for UAC and 88% and 90% for UACR. In present study, no difference was observed when comparing the performance of UAC and UACR based on a statistical comparison by McNemar test. The repeated measurements of UAC and UACR in the same individual were statistically similar and were correlated with each other. Based on these results, albumin measurements (UAC and UACR) in a RUS were considered as a valid test for screening diabetic nephropathy.

Adult↗
PubMed1997

Pharmacokinetics and toxicity of 120-hour continuous-infusion hydroxyurea in patients with advanced solid tumors.

A group of 18 patients with advanced cancer were entered on a phase I study of a 120-h continuous intravenous infusion of hydroxyurea. The dose of hydroxyurea was escalated in cohorts of patients from 1 to 2 to 3.2 g/ m2 per day. The primary dose-limiting toxicity was neutropenia, often accompanied by leukopenia, thrombocytopenia and generalized skin rash. Prophylactic treatment of patients with dexamethasone and diphenhydramine hydrochloride prevented the skin rash, but not the hematopoietic toxicities. The pharmacokinetics of hydroxyurea were studied in all patients. The steady-state concentrations of hydroxyurea were linearly correlated with the dose (R2 = 0.71, n = 18, P < 0.0001). The mean +/- SE concentrations were 93 +/- 16, 230 +/- 6 and 302 +/- 27 microM at 1, 2 and 3.2 g/m2 per day, respectively. The mean +/- SE renal and nonrenal clearances of hydroxyurea were 2.14 +/- 0.18 and 3.39 +/- 0.28 l/h per m2 (n = 16), neither of which correlated with the dose. The concentration of hydroxyurea in plasma decayed monoexponentially with a mean +/- SE half-life of 3.25 +/- 0.18 h (n = 17). The steady-state concentration of hydroxyurea was > 200 microM in all nine patients treated at 2 g/m2 per day, a dose which was well tolerated for 5 days. We recommend this dose for phase II trials in combination with other antineoplastic agents.

Adult↗
PubMed1996

Expression of bcl-2 by breast cancer: a possible diagnostic application.

Expression of bcl-2 is most commonly associated with the t(14;18) translocation present in most folicular lymphomas (1). More recently, bcl-2 oncoprotein has been identified in normal tissues and in nonhematologic malignancies. In this study, we investigate the use of bcl-2 as a marker to distinguish metastatic breast carcinoma from primary lung and gastric cancers, and we evaluate the role of bcl-2 as an independent prognostic factor in breast carcinoma and its relationship to other breast cancer markers. bcl-2 immunostains were done on 371 adenocarcinomas of the breast, lung, and stomach. Additionally, 231 samples of metastases from patients with breast or gastric cancer were evaluated for bcl-2 expression. All breast cancer tissue samples had immunohistochemical data on expression of estrogen and progesterone receptors, p53, neu/cerb2, and MIB-1. A large proportion (79.3%) of invasive breast carcinomas expressed bcl-2, whereas only 5.6% and 8.3% of pulmonary and gastric carcinomas did. Moreover, staining was moderate to intense in 70.2% of the breast cancers, compared with only one specimen of lung carcinoma (1.9%) and gastric carcinoma (0.9%) that showed moderate staining. There was agreement of bcl-2 expression between primary and metastatic sites in all specimens except one. Expression of bcl-2 in breast adenocarcinomas was significantly associated with hormone receptor positivity and low histologic grade. Nonetheless, 20.6% of bcl-2-positive specimens were estrogen receptor negative and 24.2% of bcl-2-positive specimens were progesterone receptor negative. Neither the presence nor the absence of bcl-2 expression significantly predicted disease-free survival or overall survival in patients with breast cancer. We conclude that adenocarcinomas with intense bcl-2 staining are more likely to be of breast than of pulmonary or gastric origin. We recommend the addition of bcl-2 to a panel of antibodies (estrogen receptor, GCDFP-15, and S100) that might contribute to the identification of a larger proportion of metastatic breast carcinomas, because almost one-half of the estrogen-receptor negative cancers were bcl-2 positive.

Adenocarcinoma↗
PubMed1993

Prognostic significance of immunohistochemical analysis of cathepsin D in low-stage breast cancer.

BACKGROUND: Cathepsin D is an estrogen-regulated lysosomal protease that may be overexpressed in breast cancer. Several studies based on biochemical analysis of tumor cytosol have shown that high levels of cathepsin D are associated with poor outcome in patients with breast cancer. In contrast, a few immunohistochemical studies have shown that cathepsin D positivity in breast cancer cells indicates a favorable prognostic outcome or is of no prognostic significance. METHODS: Because of the current controversy, the authors studied, using immunohistochemistry, the distribution (0 to 3) and intensity (0 to 3) of cathepsin D in Stage I and II infiltrating ductal carcinoma of the breast from 245 patients treated at the City of Hope National Medical Center, Duarte, California, from 1970 to 1986. A commercially available rabbit antiserum to purified human cathepsin D and the standard avidin-biotin complex method were used. Statistical analysis was based on a combined low (0 or 2) or high (3 to 6) score. RESULTS: A high cathepsin D score was associated with Stage II disease (P = 0.007), positive lymph nodes (P = 0.019), high nuclear grade (P = 0.005), and c-erbB-2 oncogene amplification (P = 0.013). Cathepsin D positivity was not an independent prognostic indicator of disease-free survival (DFS) or overall survival (OS). In a subgroup analysis, the presence of cathepsin D had only a modest association with predicting a shorter DFS in patients with negative lymph nodes (P = 0.072) or positive progesterone receptors (PR) (P = 0.086). CONCLUSIONS: Immunohistochemical analysis of cathepsin D, with the antiserum used in this study, is not an independent predictor of outcome in patients with breast cancer because of its strong associations with several well-established prognostic indicators.

Adult↗
PubMed1992

Pharmacokinetics and toxicity of continuous infusion (6S)-folinic acid and bolus 5-fluorouracil in patients with advanced cancer.

Twenty-seven patients with advanced cancer were entered in a phase I study of bolus i.v. 5-fluorouracil at a dose of 370 mg/m2/day for 5 days combined with a continuous i.v. infusion of (6S)-folinic acid for 5.5 days, starting 24 h in advance of the first 5-fluorouracil dose. The dose of (6S)-folinic acid was escalated in cohorts of patients from 250 mg/m2/day to a maximum of 1000 mg/m2/day. The pharmacokinetics of (6S)-folinic acid were studied in the 3 patients given 250 mg/m2/day and in 6 patients given 1000 mg/m2/day. The mean steady-state plasma concentrations of (6S)-folinic acid and its principal metabolite (6S)-5-methyltetrahydrofolate at the 250 mg/m2/day dose were 2.7 and 5.1 microM, respectively. Both concentrations were comparable to the concentrations produced when (6S)-folinic acid was administered as half of a (6R,S)-folinic acid mixture (E. M. Newman et al., Cancer Res., 49:5755-5760, 1989). At the 1000 mg/m2/day dose of (6S)-folinic acid, the concentration of (6S)-folinic acid was 15.3 microM, more than the 4-fold increase predicted by linear pharmacokinetics, while the concentration of (6S)-5-methyltetrahydrofolate was only 16.5 microM. The change in the ratio of the parent compound to its metabolite was accounted for by a decrease in the nonrenal clearance of (6S)-folinic acid, probably indicating saturation of its metabolism. The toxicities observed in this phase I trial, including stomatitis, diarrhea, neutropenia, and anemia, did not differ in nature or severity from those produced by 5-fluorouracil and (6R,S)-folinic acid when administered on the same schedule. Finally, the degree of toxicity did not appear to depend on the dose of (6S)-folinic acid over the range of doses tested.

Adult↗
PubMed1990

DSM III as a systemic culture pattern: studying intracultural variation among psychiatrists.

DSM III is viewed as embodying a pool of information pertaining to a systemic culture pattern of psychiatry and attempts are made to describe how psychiatrists understand and apply it using ideas from cognitive anthropology. Each of seven psychiatrists evaluated a group of patients in an intake setting. Seven broad categories of Axis I diagnoses were formed and the frequencies with which psychiatrists used these categories were computed. In addition, twelve arithmetical measures pertaining to the five axes of DSM III and a current functioning axis and the decision regarding disposition were also computed. Using these dependent variables, the study analyzes the similarities and differences among psychiatrists in the way they formulate intake evaluations. Psychiatrists' selections of Axis I diagnoses were highly intercorrelated but they differed greatly among themselves in the way they coded many of the axes of DSM III. Group correlations among diagnostic measures indicated a patterning among diagnostic measures and the nature of this patterning is discussed. Each psychiatrists' set of correlations among the twelve diagnostic measures was itself correlated with that of others and this showed a very high level of interpsychiatrist agreement. Deductions drawn from the cultural consensus model suggest that psychiatrists share an underlying 'grammar' that references the pool of information pertaining to DSM III.

Cultural Characteristics↗
PubMed1989

PROPOV-K: a FORTRAN program for computing a kappa coefficient using a proportional overlap procedure.

The computer program PROPOV-K allows the computation of an unweighted kappa coefficient for expressing interrater agreement in the general case in which multiple raters (not necessarily fixed in number) formulate a variable number of multiple diagnoses for each subject. PROPOV-K assesses agreement among lists of multiple diagnoses composed of nonordered categories. PROPOV-K calculates a kappa coefficient on the basis of estimating proportion of agreement between two diagnostic formulations as the ratio of the number of agreements between specific categories over the number of different specific categories mentioned in the two diagnostic lists. When multiple raters formulate a variable number of multiple diagnoses for each subject, the use of a kappa coefficient has been limited to researchers since there are no generally available computer programs. The purpose of this paper is to present a FORTRAN computer program allowing the computation of a kappa coefficient for the case mentioned above and to illustrate its use with examples respectively involving multiple psychiatric and multiple physical diagnoses.

Algorithms↗
PubMedDate not supplied

Explaining diagnostic complexity in an intake setting.

A one patient-one illness paradigm is implicit in the history and theory of psychiatry, and in basic research. Yet, in clinical practice and treatment populations in general, more than one diagnosis per patient is frequently encountered. How clinicians formulate comorbidity by means of DSM-III has rarely been investigated. In this study, the ideas of clinical condition and that of its diagnostic complexity are used to analyze descriptive features of a large number of patients seen in an intake setting. Axis I of DSM-III is used to measure diagnostic complexity. Complexity is analyzed in relation to demographic variables, to ratings entered in the remaining axes of DSM-III formulations, to symptom levels of patients, and to decisions involving disposition. Results indicate that analysis of diagnostic complexity by means of DSM-III yields a definable structure and that it can be related meaningfully to clinical factors. The idea of information uncertainty in diagnosis, i.e., the opacity versus transparency of a clinical condition, is also used to explain results. The ideas introduced and studied are shown to have value for social psychiatric research.

Adaptation, Psychological↗