Podocyte Expression of Osteopontin and FSP-1/S100A4 in Human Crescentic Glomerulonephritis

BACKGROUND: Osteopontin (OPN) is a cytokine associated with a cell-matrix via integrins. Fibroblast specific protein-1 (FSP-1), known as S100A4, has been implicated in cell migration by non-muscle myosin. We investigated whether the role of OPN and FSP-1/S100A4 expression in their contribution to the podocyte phenotype change to form podocyte bridge and cellular crescent. METHODS: Glomerular expression of OPN and FSP-1/S100A4 in renal biopsies of 16 patients with crescentic glomerulonephritis (CrGN) and 13 normal renal biopsies were studied by immunohistochemistry. RESULTS: The expression of OPN and FSP-1/S100A4 was increased in the podocytes of glomeruli, with and without crescents, in patients with CrGN. Neither OPN nor FSP-1/S100A4 was expressed in glomeruli from the normal controls (p<0.01). A significant positive correlation was found between the expression of OPN in glomerular tufts and cellular crescents, and the expression of OPN and FSP-1/S100A4 in glomerular tufts (p<0.05). CONCLUSIONS: The results suggest that OPN plays a role in early podocyte attachment to Bowman's capsule, and FSP-1/S100A4 potentiate podocyte contribution to cellular crescent formation by inducing cellular migration and growth.

Significance of Osteopontin Expression in the Progression of Human Focal Segmental Glomerulosclerosis

BACKGROUND: Osteopontin (OPN) is a cytokine related to cell-matrix adhesion and cell survival and is expressed in the distal convoluted tubules in normal adult kidneys. Only one in vitro study has investigated the role of OPN in mechanically stretched podocytes and their actin cytoskeleton rearrangement. METHODS: Glomerular OPN expression was investigated in biopsies from patients with human idiopathic focal segmental glomerulosclerosis (FSGS) (n = 25) and in normal renal biopsies (n = 16) by immunohistochemistry. RESULTS: OPN was expressed in the podocytes from patients with FSGS. OPN expression increased in podocytes from both non-sclerotic hypertrophic and sclerotic glomerular tufts in patients with FSGS compared to the podocytes in normal controls. CONCLUSIONS: The results suggest that OPN plays a role in the early adaptive response of podocytes to the increased mechanical load caused by glomerular hypertrophy preceding FSGS. OPN was involved in cell-matrix adhesion and influenced the detachment delay of podocytes from the glomerular basement membrane and apoptosis.

Effects of Lower Extremity Exercise Program on Muscle Strength and Flexibility in Women with Knee Osteoarthritis / 기본간호학회지

PURPOSE: The purpose of this study was to determine the effects of a lower extremity exercise program on muscle strength and flexibility in women with knee osteoarthritis. METHOD: This study was conducted using a non-equivalent control group pretest-posttest design. The participants were 35 women with knee osteoarthritis. The experimental group performed the lower extremity exercise program, which was an adapted BeHaS exercise program developed by Kim(2006). It consisted of approximately 65-130 minutes per one session, two days a week, for twelve weeks. Lower extremity muscle strength was measured by the Seated Leg Press Machine (TY-H2217, made in Korea), back muscle strength by back muscle strength scale (TKK 5402, made in Japan) and flexibility, by Sit and Reach tester (01285, U.S.A). Data were gathered from September 2005 to March 2006. Frequency, chi-square test and t-test were used to analyze the data. SPSS Win 11.0 was used to assist analysis. For normal distribution of data, Kolmogorov-Smirnov test was done. RESULTS: There were statistical differences in the mean strength of both legs together, strength in leg with more pain(p=.044; p=.046), sit and standing time (p=.007), and back strength (p=.021). CONCLUSION: Based on these results, it can be concluded that a lower extremity exercise program can help improve lower extremity muscle strength in women with osteoarthritis.

Osteopontin Expression and Its Prognostic Significances in Human Renal Cell Carcinoma

BACKGROUND: Osteopontin (OPN) is a glycoprotein and it participates in cell-cell and cell-matrix interactions. In vitro studies suggest that the OPN expression is associated with tumor metastasis, and especially with the metastasis of osteotropic tumors originating in breast, prostate and lungs. Since no human tissue study has suggested the means by which OPN participates in the tumorigenesis, angiogenesis, progression and metastasis of renal cell carcinoma (RCC), we evaluated the expression and prognostic significance of OPN in RCC. METHODS: Immunohistochemistry was performed with using the primary antibody for OPN on the archival paraffin-embedded tissue microarray specimens from 51 RCC patients who underwent radical or simple nephrectomy. RESULTS: In the normal kidney specimens, OPN was expressed in a few compressed distal tubules adjacent to the RCCs. In RCCs, the OPN expression was elevated in larger tumors (p<0.05) and in the tumor with low microvessel density (p<0.01). In the present study, univariate analysis indicated that stage, tumor size, lymph node and distant organ metastasis are significant prognostic factors for disease free survival (DFS) in RCC patients (p<0.01), but OPN is not (p=0.0661). Multivariate analysis indicated lymph node metastasis is the independent prognostic indicator of DFS (p<0.05). CONCLUSION: Though this study has statistical limitations, these results suggest OPN plays a role in tumor progression and metastasis and it may act as a potential prognostic indicator to predict the prognosis of RCC patients.

Expression Patterns of Tumor Related Proteins for Differential Diagnoses of Intrahepatic Adenocarcinomas

Background : Differential diagnoses of intrahepatic adenocarcinomas (IHAC) play an important role in the detecting primary sites and the determining type of treatment and overall prognosis of the patient. However, histopathologic findings alone have limitations of differential diagnoses of IHAC. Methods : To clarify which tumor related proteins (TRP) are useful for differential diagnoses of IHAC, TRP expression were investigated immunohistochemically, using MUC5AC, MUC2, mAb 91.9H, MUC1, and pS2, and by high iron diamine (HID) staining in 61 clinically confirmed IHACs. Results : MUC5AC (9/18, p0.05) displayed the most frequent expression in cholangiocarcinomas, and MUC2 (11/18, p0.05) was expressed more often in pancreatic adenocarcinomas than other IHAC, while MUC2 and 91.9H were not expressed at all in pancreatic adenocarcinomas. The positivity of several TRP did not correlate with tumor differentiation. Conclusions : MUC5AC, MUC2, mAb 91.9H, and HID may be useful in differentiating cholangiocarcinomas from colorectal adenocarcinomas.

Expression of CD44 Isoforms and Its Significance in Renal Cell Carcinoma

Background : CD44 is a transmembranous glycoprotein that participates in cell-cell and cell-matrix interactions, and it also contributes to cell migration. In vitro studies have suggested that the expression of CD44 isoforms is associated with tumor metastasis. Since it is not clear whether the CD44 isoforms play a role in the tumorigenesis, differentiation, progression or metastasis of renal cell carcinomas (RCCs). Methods : We performed immunohistochemistry with primary antibodies for the standard CD44 (CD44s) and the CD44 variant exon 6 (CD44v6) on the archival paraffin-embedded tissue microarray (TMA) specimens from 51 RCC patients. Results : In the normal kidney, the expressions of both CD44s and CD44v6 were negligible. The CD44s expression was increased in accordance with the tumor size (p<0.01), but it was not related to the microvessel density (MVD). No CD44v6 expression was observed in all RCC cases. Univariate analysis indicated that stage, tumor size, lymph node metastasis and distant organ metastasis were the statistically significant prognostic factors for disease free survival (DFS) (p<0.01), and the multivariate analysis proved that stage (p<0.01) and tumor size (p<0.05) were the independent prognostic factors for DFS. Conclusions : Our results suggest that CD44s, but not CD44v6, plays a role in tumor progression and it could be a potential prognostic factor for patients with RCCs.

An Analysis for Angiotensin Converting Enzyme Gene Polymorphism in Formalin-fixed, Paraffin-embedded Tissues from Patients with Sarcoidosis

BACKGROUND: Sarcoidosis is a systemic disease characterized by nonnecrotizing granulomas involving the lung and hilar lymph nodes. Serum angiotensin converting enzyme (sACE) levelsin patients with sarcoidosis have been implicated as an indicator of granuloma burden.Recently, it has been found that ACE gene insertion/deletion (ID) polymorphism affects sACE levels in healthy individuals. Moreover, reported sACE levels were highest in the deletion/deletion(DD) genotype. Previous studies to investigate the distribution of ACE genotypes accordingto ethnic groups have revealed various results and have caused controversy. METHODS: Polymerase chain reactions were performed to determine the ACE genotypes in fifteen formalinfixed, paraffin-embedded tissues from patients with sarcoidosis. RESULTS: The distribution of ACE gene (I/D) polymorphism in patients with sarcoidosis was significantly different from that in normal controls. The DD genotype was more frequent in patients with sarcoidosis than in thenormal controls. The D allele frequency was also higher in patients with sarcoidosis than in thenormal controls. The relative risk of sarcoidosis was higher in DD homozygotes. CONCLUSIONS: These results suggested the ACE gene I/D polymorphism may play an important rolein the pathogenesis and progression of sarcoidosis.

The Effect of Aquatic Exercise Program on Body Weight, Muscle Strength and Flexibility in Healthy Middle-aged Women / 기본간호학회지

PURPOSE: Aquatic exercise program is known to have positive effects for health maintenance and improvement in inpatients with arthritis. Aquatic exercise program could be a way to obtain wellness in middle-aged women. However, there have been few studies to evaluate physical function. The purpose of this study was to identify the effects of aquatic exercise on physical health such as body weight, BMI, muscle strength (grip strength, pinch pressure), and flexibility in healthy middle-aged women. METHOD: The subjects of the study were fifty healthy middle-aged women (40-59 years) who had no experience with exercise. Twenty five subjects were assigned to the experimental group and 25 to the control group. An aquatic exercise program which consisted of approximately one hour of exercise in the water, two days per week, for six weeks was given to the experimental group. Data were gathered from October 2000 to April 2001 using a questionnaire and physical function measure tool (pinch pressure, grip strength, weight, centimeter ruler). Data were analyzed with the SPSS win 10.0 using frequency, t-test, x2 test, paired t-test, and ANCOVA. RESULT: The results of this study are as follows: There were significant differences in body weight, BMI, right, left grip strength and right and left pinch pressure between the two groups. CONCLUSION: From these results, it is concluded that the aquatic exercise program for healthy middle-aged women can be effective in increasing physical health in these women.

Small Cell Carcinoma of the Ureter with Squamous Cell and Transitional Cell Carcinomatous Components associated with Ureteral Stone

We report a case of primary small cell carcinoma of the ureter with squamous cell and transitional cell carcinomatous components associated with ureteral stone, which is unique in that the patient has remained free of tumor recurrence for 36 months after the surgery without adjuvant chemotherapy or radiotherapy. A 60-yr-old man presented himself with a right flank pain. Computed tomography revealed an ill-defined mass and a stone in the lower one third of the right ureter, and hydronephroureterosis above the stone-impacted site. The patient underwent right nephroureterectomy and stone removal. Upon gross examination, a 3.8 x 1.8 x 1.2 cm white and partly yellow mass was noted in the anterior part of the ureter, resulting in indentation of the ureteral lumen on the posterior side. Light microscopic examination revealed that the mass was mainly composed of small cell carcinoma, and partly squamous cell and transitional cell carcinomatous components. The overlying ureteral mucosa and renal pelvis also contained multifocal dysplastic transitional epithelium and transitional cell carcinoma in situ. There was no vascular invasion, and the surgical margins were free of tumor. The small cell carcinomatous component was positive for chromogranin, neuron specific enolase, synaptophysin, and pancytokeratin but negative for high molecular-weight cytokeratin (K-903) by immunohistochemistry.

Immunohistochemical Expression of p53, p21, and mdm2 Proteins in Human Papillomavirus Positive and Negative Invasive Uterine Cervical Carcinomas

BACKGROUND: In the uterine cervical carcinoma, the inactivation of p53 protein by human papillomavirus(HPV) E6 protein has been reported to play a greater role in carcinogenesis than the mutation of the p53 gene. Therefore, the mutation of the p53 gene is rare. p21 and mdm2 proteins are induced by wild-type p53 protein and are involved in the cell cycle regulatory mechanism. METHODS: Immunohistochemical staining for p53, p21 and mdm2 proteins was performed in 26 HPV-positive and 13 HPV-negative invasive cervical carcinomas together with 5 non-neoplastic cervical tissues. RESULTS: The frequencies of the expression of p53, p21 and mdm2 proteins were 82.1%, 84.6% and 66.7%, respectively. The expression of p53 protein was less frequently demonstrated in HPV-positive cases than HPV-negative cases, which was statistically a negative correlation(p=0.018). The expression of p53 and p21 proteins was statistically significant(p=0.000). CONCLUSIONS: p53, p21 and mdm2 proteins were highly expressed in both HPV-positive and HPV-negative cervical carcinomas. Significantly higher expression of p53 protain in HPV-negative cases necessitate a further study for investigating the role of p53 protein accumulation in carcinogenesis of HPV-negative cervical carcinomas. The relationship between the expression of p53 protein and p21/mdm2 proteins may indicate that p21 and mdm2 proteins also have a role in carcinogenesis, where p53 protein plays a fundamental role.

A case of epidermoid cyst of the intrapancreatic accessory spleen

A 54-year-old woman presented with a huge palpable mass on left upper quadrant of the abdomen. After preoperative work-up, a cystic disease of pancreatic tail or accessory spleen was initially suspected. We performed exploratory laparotomy and resected both the spleen and a 15 x 11 cm-sized huge cystic mass containing a part of solid component which extended continuously to the pancreatic tail. The solid component, comprising the upper portion of the resected cyst, was reddish brown and granular like as normal splenic tissue. The inner surface of the cyst was smooth and was filled with yellowish white material. Histologic examination showed an epidermoid cyst originating in the accessory spleen of the pancreatic tail lacking hair or skin appendages.

Prostatic Intraepithelial Neoplasia in Transurethral Resection Specimens On serum PSA and histologic findings

Prostatic intraepithelial neoplasia (PIN), which is divided into low and high grade, has different clinicopathologic significance. We reviewed 158 prostatic tissues, which consisted of 144 cases of nodular hyperplasias and 14 cases of adenocarcinomas, to evaluate incidence of PIN, its histologic finding, and its clinical significance. Ten cases of PIN, 4 low grade and 6 high grade, were found. Four cases of low grade PIN (LPIN) and five cases of high grade PIN (HPIN) were associated with nodular hyperplasia. Only one case of HPIN occurred in carcinoma. The constant histologic findings of LPIN were nuclear stratification and nucleomegaly. The most prominent characteristics of HPIN were hyperchromasia and prominent nucleoli. Anisonucleosis was not so helpful for differential diagnosis between LPIN and HPIN. Basal layer disruption was present in one case of high grade PIN associated with adenocarcinoma, and important for the differentiatial diagnosis of cribriform HPIN from the cribriform adenocarcinoma. There was no significant difference in age incidence between the two groups with the mean age of 70.9 years in nodular hyperplasia and 69.4 years in adenocarcinoma. Serum PSA level was significantly different between the two group with the mean PSA value of 11.03 ng/ml in nodular hyperplasia and that of 73.76 ng/ml in carcinoma (p=0.000). However, PSA values between "nodular hyperplasia only" group and "PIN associated nodular hyperplasia" group were not significantly different. PIN association changed neither age distribution nor serum PSA level. During the follow up period, no adenocacinoma has occurred in the cases having PIN although serum PSA level has elevated in some cases. One case of adenocarcinoma associated with HPIN developed in the nodular hyperplasia patient. Although PIN did not increase the possibility of subsequent prostatic adenocarcinoma in transurethral resection specimens, it could not be excluded that PIN was a precursor of prostatic adenocarcinoma.

Mechanism of Glomerular Basement Membrane Thickening in Human Membranous Nephropathy / 대한신장학회잡지

Membranous nephropathy is the most common cause of nephrotic syndrome in adult. To investigate the molecular mechanisms which underlie thickening of glomerular basement membrane, we analyzed alpha1(IV) collagen, alpha4(IV) collagen, laminin A, laminin B1, laminin B2, s-laminin, fibronectin, TGF-beta1 and TGF-beta2 mRNA expression in 21 renal biopsies with membranous nephropathy using in situ hybridization. In addition, 7 renal biopsies with no detectable abnormalities were used as control. In membranous nephropathy, the numbers of glomerular visceral epithelial cells expressing alpha1(IV) collagen, alpha4(IV) collagen, s-laminin and TGF-beta1 mRNA were significantly larger than in controls(p<0.05). Laminin A, laminin B1, laminin B2, fibronectin, and TGF-beta2 mRNA were rarely expressed in membranous nephropathy and in control group. The number of TGFbeta-1 mRNA expressing cells/glomerular cross-section correlated to that of alpha1(IV) collagen mRNA expressing cells (p< 0.05). These results indicate that increased presence of glomerular basement membrane proteins in spikes of membranous nephropathy is associated with enhanced mRNA expression of those proteins in the glomerular visceral epithelial cells. Subepithelial deposits in membranous nephropathy stimulate glomerular visceral epithelial cells to produce TGF-beta1, which in turn could mediate the expression of glomerular basement membrane protein genes by glomerular visceral epithelial cells.

Type IV Collagen mRNA Expression in Human Membranous Nephropathy

Human membranous nephropathy (MN) is morphologically characterized by subepithelial immune complex deposits and progressive thickening of glomerular basement membranes (GBM). Studies have suggested that the enhanced secretion of classical and novel type IV collagen chains in MN contributes to spike formation and the novel type IV collagen chain is particularly related to thickening of GBM. It is unclear whether the increased accumulation of extracellular matrix (ECM) proteins in GBM is due to the increased mRNA expression for type IV collagen in glomerular visceral epithelial cells (GECs). To answer this question, we analyzed seven renal biopsies of patients with idiopathic MN using in situ hybridization. In MN, the number of GECs expressing mRNA for alpha1(IV) collagen was 2.82+/-1.80/glomerular cross section (gcs), and the number expressing mRNA for alpha4(IV) collagen was 8.42+/-2.85/gcs. The number of GECs expressing mRNA for alpha4(IV) collagen was significantly larger than that of alpha1(IV) collagen mRNA. The expression of mRNA for these ECM proteins in normal controls was negligible. These results suggest that subepithelial immune complexes stimulate the gene expression of alpha1(IV) collagen and alpha4(IV) collagen in glomerular GECs which, in turn, increase the secretion of ECM proteins and contribute to the thickening of GBM in MN.

Correlation between expression of matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) and angiogenesis in colorectal adenocarcinoma

Matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), which degrade extracellular matrix, are believed to play a crucial role in tumor invasion and metastasis. Angiogenesis is also perceived as an important step in tumor growth and metastasis. To investigate the expression of MMPs and the correlation between the expression of MMPs and angiogenesis in colorectal adenocarcinoma, we studied 72 cases of colorectal adenocarcinoma in Inha University Hospital from 1996 to 1997. We evaluated the expression of MMPs by immunohistochemistry and angiogenesis by counting the microvessels. The expression of MMP-2 was increased according to the Astler-Coller stage (p< 0.05). Angiogenesis in the metastatic group was higher than that of the localized one (p<0.05). The expression of MMP-2 positively correlated with angiogenesis (p<0.05), and marked expression of MMP-9 positively correlated with angiogenesis (p<0.05). The present results suggest that the expression of MMP-2 provides clues for tumor progression and angiogenesis provides significant information to predict whether metastasis is present in colorectal adenocarcinoma.

A Case of Chronic Renal Failure, Caused by IgA Nephropathy Combined with Polycythemia Vera / 대한신장학회잡지

Patients with chronic renal failure, generally, sufferred from normocytic normochromic anemia caused by decreased level of erythropoietin. But, secondary erythrocytosis has been reported in patients with several renal diseases; renal artery stenosis or throm- bosis, polycystic kidney disease, bilateral hydronephrosis, etc. We report one case of chronic renal failure combined with polycythemia vera. The case was 32 year-old man whose chief complaints were dyspnea, back pain, itching sensation, headache. 6 month ago, the laboratory examination showed only proteinuria and hematuria without deterioration of renal function. The renal function was aggravated with an accelerated course, and bone marrow examination revealed hypercellularity (erythroid predominance), and renal biopsy showed the finding of the end stage of renal disease which may be originated from IgA nephropathy.

Hardiness: Determinants of Psychological Distress from Stress / 간호학회지

This study was understand in order to examine the effect of hardness on stress-causing factors, defined in this study as burnout in nursing. The subjects were 248 nurses working in three general hospitals in Taejon. The instruments used for this study were a survey of general characteristics, modified Health-Related Hardiness Scale(HRHS) (25 items), job stress scale (63 items), and burnout scale(20 items). Analysis of data was done through the mean, percentage, Person correlation coefficient, and stepwise multiple regression done with a SAS program. The results of this study are as follows. 1) The average item score for the job stress was high at 4.44. In the subcategories, the highest degree of stress was night duty(5.11), and work overload(4.70), responsibility for extra affairs(4.70), conflict in nurse-doctor relationships(4.69), and low reward (4.63) in that order. 2) In the stepwise multiple regression analysis, hardiness(11.55%) was a significant determinant of burnout along with job stress(17.24%) and job duration(12.94%). The results of this study show that hardiness has an effect on psychological distress caused by stress.

Malignant Rhabdoid Tumor of the Cerebellum in an Adult: A case report

Malignant rhabdoid tumor (MRT) is a rare and highly aggressive neoplasm of infancy and childhood. Although it was originally described and most frequently reported in the kidney, it may occur in various extra-renal sites such as the liver, thymus, and soft tissue. In the last decade primary central nervous system (CNS) MRTs have been reported in both the supra- and infratentorial compartments. Patients with CNS MRT were generally below the age of two and reports in adults are extremely rare. This is a case of primary cerebellar MRT in a 24-year-old woman, who had presented with intermittent headache, vocal cord palsy, and cerebellar dysfunctions such as abnormal finger to nose test and tandem gait. By magnetic resonance imaging scan, a well-enhancing solid mass was demonstrated at the posterior fossa filling the 4th ventricle, which extended into the medulla and cervical cord via the foramen of Magendie. Histologically, the monotonous polygonal tumor cells were arranged in diffuse sheet with occasional hemorrhagic necrosis. The nuclei were vesicular and eccentrically located due to eosinophilic, PAS-positive, intracytoplasmic inclusions with prominent nucleoli. They were diffusely or focally immunoreactive for vimentin, neurofilament, cytokeratin, GFAP, synaptophysin, and smooth muscle actin, while epithelial membrane antigen and desmin were negative. Ultrastructurally, the polyhedral tumor cells were densely packed with primitive intercellular junctions. Scanty fibrillar intermediate filaments were intermingled with cellular organelles. Postoperatively, craniospinal irradiation and systemic chemotherapy have been done and she has been free of tumor recurrence during the 13 months' follow-up periods.

Correlation between VEGF Expression and Angiogenesis in Advanced Gastric Carcinoma / 대한암학회지

PURPOSE: VEGF is thought to be an important angiogenic factor playing significant a role in the aggressiveness of malignant tumor by stimulating neovascularization. We morphologically investicated the tumor angiogenesis in terms of the presence of VEGF expression in advanced gastric carcinoma. MATERIALS AND METHODS: We performed immunohistochemical stains for VEGF, CD 34, and MIB-1 (Ki-67) on the 51 paraffin-embedded tissue sections. The degree of angiogenesis was determined by counting microvessel densities and their Ki-67 labelling indices of endothelial cells within the tumors. We evaluated the correlation between the expression of VEGF, angiogenesis and clinicopathologic factors such as histologic differentiation, depth of invasion, and lymph node metastasis. RESULTS: Immunoreactivity for VEGF revealed positivity in 34 out of 51 cases (66.7%). Microvessel densities and Ki-67 labelling indices of endothelial cells reflecting angiogenesis were higher in VEGF-positive tumors than VEGF-negative tumors. There were no conelations between VEGF expression, histologic differentiation and the depth of invasion. We failed to evaluate the conelation of VEGF expression and lymph node metastasis. CONCLUSION: This study suggests that VEGF expressian is closely related to tumor asso- ciated angiogenesis in advanced gastric carcinoma. Considering that tumor growth depends on angiogenesis, therapies reducing VEGF may be a means of inhibiting angiogenesis and tumor aggressiveness.

Application of the Revised Case Matrix Format to Tutorial in Pathology Teaching: An Interim Approach toward Problem-Based Learning under Traditional Curricular Structure

This paper describes a student-centered case study program concerning the tumor pathology course for first year students in medical school under the traditional curricular structure. A traditional, discipline-oriented, lecture-laboratory approach was partly modified by introducing a tutuorial session using a modified case matrix format during the laboratory hours without altering the general scheme of the existing system. Small group tutorial sessions were set with the development of learning objectives emphasizing clinicopathologic reasoning and early exposure to future practical presentation which was followed by the large class session; each tutorial was supplied with a short clinical history, gross kodachrome slides, and microslides. The session for problem identification was replaced by proving a series of instructor-designed questions for both pathology and interdisciplinary correlation during which pedagogical implication was stressed the most. Student's active participation, development of self learning skill and vigorous teaching-learning process among students, and motivation/relevance for forthcoming pathology study were among the benefits conferred by this modification. We conclude that this approach is an interim step to meet the advantages of problem-based learning even in a traditional curricular structure.