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Background: The postoperative intrahepatic recurrence of hepatocellular carcinoma (HCC) is high. It is difficult to distinguish whether the recurrence is metastatic or new primary lesion. To determine the malignant potential of HCC itself, we analyzed the risk factors associated with portal venous invasion since this is direct evidence of tumor invasiveness., Methods: Two hundred and thirty-two patients who underwent curative hepatectomy for HCC without preoperative treatments were included in this study, because preoperative treatment caused the tumor to undergo a variety of histologic change. We analyzed the risk factors linked to portal venous invasion by both univariate and multivariate analyses., Results: In an univariate analysis, tumors larger than 3 cm, high histologic grade (III or IV), the presence of fibrous capsule, necrosis, mitotic rate of more than 4/10 high power fields, peliotic change, presence of tumor giant cells, high platelet count, low level of indocyanine green retention rate at 15 minutes, and the absence of cirrhosis were significantly correlated with portal venous invasion. In multiple stepwise logistic regression analysis, tumors larger than 3 cm, high histologic grades, and the presence of fibrous capsule were strong predictors of portal venous invasion by HCC., Conclusions: Because the blood vessels of the fibrous capsule were frequently invaded by cancer cells, it may have been possible to prevent postoperative metastatic recurrence if HCC were resected before becoming large enough to have a fibrous capsule.

The immunohistochemical expression of bcl-2 and p53 proteins was evaluated in formalin-fixed, paraffin-embedded surgical specimens from 212 patients with primary gastric lymphoma. bcl-2 protein was found to be expressed in 145 specimens (68%). Among the 179 specimens with B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), bcl-2 positivity decreased significantly as the histological grade advanced; bcl-2 was expressed in 93% of low-grade tumors, 88% of mixed-grade (low-grade with a focal high-grade component) tumors, and 44% of high-grade tumors (Cochran's linear trend test; P<.001). p53 protein expression was detected in 43 of 212 cases (20%). Among the B-cell MALT lymphomas, p53 positivity increased significantly as the histological grade advanced; p53 was expressed in 6% of low-grade tumors, 12% of mixed-grade tumors, and 31% of high-grade tumors (Cochran's linear trend test; P<.001). An inverse correlation was observed between the expression of bcl-2 and p53 in all 212 lymphomas (gamma = -0.531; P<.05) as well as in all 179 B-cell MALT lymphomas (gamma = -0.671; P<.01). Although the bcl-2 expression did not correlate with the patient survival, the p53 positive cases showed a significantly poorer prognosis compared with the p53 negative cases (log-rank test; P<.05). These results suggest that the expression of bcl-2 and p53 may, therefore, be associated with the transition from low-grade to high-grade tumors in primary gastric lymphoma.

To understand the role of vascular endothelial growth factor (VEGF) in placental development, we examined immunohistochemically 56 placentae ranging from 6--41-weeks gestation using rabbit antibody to a synthetic multiple antigen peptide (MAP), composed of N-terminal amino acid residues 1--20 of human VEGF. In the present study, syncytiotrophoblast and invading extravillous trophoblasts ubiquitously expressed VEGF throughout gestation. However, the expression of VEGF in syncytiotrophoblasts was uneven in the first trimester and most intense at the sprouting sites. In addition, some stromal cells in the villi and decidual cells were also positive in the first trimester. A morphometrical analysis of the ratio of the VEGF-positive cell area to the capillary area in the terminal villi statistically revealed a critical point of change at 16 weeks' gestation. These results provide further evidence to support the hypothesis that VEGF, locally expressed by trophoblasts, stromal cells in villi and decidual cells, may play an important role in the physiological growth and function of the vascular system in the villous stroma and basal plate during placental development and maturation.

We titrated antibody to hepatitis C virus (anti-HCV) core of serum samples from 57 patients with chronic HCV infection, in an attempt to clarify the relationship between the level of HCV RNA and the outcome of interferon treatment. The patients studied were positive for both anti-HCV, by second-generation assay, and HCV RNA, by polymerase chain reaction, and had been treated with interferon for six months. Of the 57 patients, HCV RNA was eliminated in 16 by the time of discontinuation of interferon treatment (CR); in 19 this elimination was transient (PR) and for 22 elimination was nil (NR). The low HCV RNA level was accompanied by high titers of anti-HCV core while high HCV RNA levels were accompanied by low titers of anti-HCV core, with an inverse correlation (r = -0.322, P < 0.05). The mean titer of anti-HCV core before interferon treatment was 324 units in CR, 205 in PR, and 168 in NR, with a correlation ratio of 0.382 (P < 0.05). A decreased titer (more than 50%) was found in 68% of the CR. At the time of six-month follow-up, the anti-HCV core titers of CR had decreased by more than 50%, compared to pretreatment titers, while in PR and NR, there was an increase to above the pretreatment titers, without increases in HCV RNA levels or worsening of the hepatitis. In conclusion, quantitative assay for anti-HCV core is useful to assess the status of HCV replication.

Background/aims: Postoperative intrahepatic recurrence of human hepatocellular carcinoma is high. Recently, the relationship between proliferating cell activity in the cirrhotic liver and occurrence or recurrence of hepatocellular carcinoma has been reported., Methods: One hundred two resected cases of small hepatocellular carcinoma of < 3 cm in diameter without venous invasion or intrahepatic metastasis were examined to ascertain the factors affecting postoperative intrahepatic recurrence., Results: Cumulative intrahepatic recurrence rates at 1, 3, and 5 years after surgery were 12.0%, 57.2%, and 67.6%, respectively. The log-rank test indicated that serum albumin levels of < 3.7 g/dL, alanine aminotransferase levels of more than 54 IU/L, active inflammation in the nontumorous portion, and high proliferating cell nuclear antigen labeling index in the nontumorous portion (> 23.2%) were significant risk factors for recurrence. Tumor factors, including tumor size, histological grade, or alpha-fetoprotein level, were not significant risk factors. Cox's proportional hazard model identified that serum albumin level and alanine aminotransferase level were independently associated with intrahepatic recurrence after hepatectomy., Conclusions: This study suggests that the principal cause linked to either a recurrence or a second new growth of hepatocellular carcinoma in the remnant liver after hepatectomy was the state of the underlying liver parenchyma as well as other tumor factors per se.

The Vogt-Koyanagi-Harada (VKH) syndrome is a form of recurrent uveitis with often a poor long-term visual acuity. The risk factors for recurrence of the VKH syndrome were investigated statistically by using a multiple logistic regression model. The clinical data of 87 patients were used for the statistical analysis. Among them, 58 patients (66.8%) had no recurrences, while 29 patients (33.3%) had recurrences. By multiple logistic regression analysis, dysacousia (p<0.01), cutaneous manifestations (p<0. 05), prodromal symptoms (p<0. 05), onset to treatment interval (days) (p<0. 05) and retinal detachment (p<0. 01) were significantly and independently associated with the recurrence. The Relapse Score was constructed by using a logistic model as follows: Relapse Score=+1. 459X (Dysacousia) + 1. 458x (Cutaneous manifestations) +0. 032x (Onset to treatment interval) -1. 637x (Prodromal symptoms) -1. 773x (Retinal detachment)+1. 247. It is supposed that the Relapse Score might be helpful for predicting the clinical course and modifying the dose or duration of systemic steroid therapy of the patients with the VKH syndrome.

Immune cell subsets, when measured by two-color flow cytometry in a population of 129 hemodialysis patients, showed significant variance from normal values. Lymphopenia, decreased absolute counts, and altered percentage values of immune cells were found. Increased proportions of CD3+, T cell receptor (TCR) alpha beta + cells and CD4+ T lymphocytes were present. An abnormally high percentage of a subset of activated TCR alpha beta + cells (alpha beta + DR+) was also seen in hemodialysis patients. The proportion of B lymphocytes was found to be significantly lower as compared with controls. Relative values for TCR gamma delta+cells, both for activated (gamma delta + DR+) and nonactivated (gamma delta + DR-) subsets, as well as for CD8+ lymphocytes and natural killer cells did not vary from those of normal controls. Also, the CD4+/CD8+ ratio showed no significant change. Analysis of absolute counts of the investigated immune cell populations revealed significantly decreased numbers for the majority of subsets, as a result of the preexisting lymphocytopenia, characteristic of end-stage renal disease. We conclude that profound quantitative alterations of immune cells, including TCR+T cells subsets, exist in hemodialysis patients. These account, at least in part, for the immune dysregulation associated with chronic renal failure.

Objective: To determine markers predictive of effective interferon treatment for patients with chronic hepatitis C virus (HCV) infection, we studied 80 Japanese patients treated for 6 months with natural interferon-alpha., Methods: Serum samples were tested for HCV RNA by two-stage polymerase chain reaction (PCR). HCV RNA were grouped into four genotypes by amplification of core-gene sequences by PCR with type-specific primers, and the level of HCV RNA was measured by competitive PCR. HCV RNA was detected in all patients before the interferon treatment. For the purposes of this study, a complete response was defined as the elimination of HCV RNA for at least 6 months after termination of the treatment., Results: HCV RNA was eliminated from the sera of 27 patients (33.8%) at the termination of the interferon treatment, and the elimination was sustained throughout a 6-month follow-up (complete response). Four of eleven variables proved to be associated with a complete response when assessed by univariate analysis. With multiple logistic regression analysis assessment, however, only two variables (HCV RNA level (p < 0.001) and genotype (p = 0.048)) were significant., Conclusion: These results suggest that factors associated with the HCV infection are more important than patient characteristics for effective interferon treatment of patients with chronic HCV infection and that a low level of HCV RNA and HCV of genotype III are useful predictors of a complete response.

This paper describes the design of a Microsoft Excel Program which interactively creates attractive and outstanding survival curves. This program enables medical researchers to easily create quality presentation graphs of survival curves and obtain high quality slides and prints, which can be inserted in papers or used directly at medical meetings. Through the use of vertical bars, this program can display the exact points where censored cases occur on survival curves, making it possible to monitor censoring patterns between groups. Furthermore, this program can also create survival curves based on the proportional hazards model for specific patterns of covariate values, given estimated regression coefficients and baseline survival function. This program may be a most useful and effective tool in creating medical research papers containing survival analysis.

We titrated 277 hepatitis C virus (HCV) antibody-positive serum samples from 235 volunteer blood donors as well as from 42 outpatients of a hospital for elderly people and studied the relation of the titre of HCV antibody to the presence of HCV RNA, of antibody to C100 protein (anti-c100) and of antibody to GOR epitope (anti-GOR). Liver dysfunction was measured also. Of 177 HCV RNA-positive serum samples, 87 were tested for the degree of HCV viraemia by means of a competitive assay. Among the 277 samples, prevalences of HCV RNA, anti-c100, anti-GOR and liver dysfunction were 63.9%, 71.8%, 75.7% and 17.5%, respectively. The prevalence of HCV RNA became higher as the titre of HCV antibody increased. The titre tended to increase with age but the tendency was not statistically significant. The mean titre was higher in females (2(10.4 +/- 1.8)) than in males (2(9.4 +/- 2.2)) (P < 0.01). In the HCV RNA-positive serum samples, the HCV antibody titre was significantly higher in the anti-c100-positive samples than in the negative ones. This difference between the positive and negative samples, however, was not statistically significant for anti-GOR and liver dysfunction. Low degrees of HCV viraemia were accompanied by high titres of HCV antibody while high degrees of HCV viraemia went with low titres of HCV antibody. The study revealed that titres of HCV antibody were higher in females and the degree of HCV viraemia correlated inversely with the titre of HCV antibody.

In this paper, we discuss the organizational structure for the conduct of statistical activities at medical Colleges and Universities. Here, we have particularly focused on two significant statistical activities, i.e., statistical consultation and research. The consulting service for medical researchers consists of practical statistical analysis, instruction on computer manipulation and software, response to reviewer's comments and statistical design of prospective studies. From our various experiences, we describe the actual implementation of statistical consultations for medical researchers. It has played an important role in supporting medical research. In addition, we also outline some research, with respect to new ways of applying statistics in medical science. This paper concludes that it may be practical for the existing computer center or department of medical informatics, in charge of the computing service, to conduct statistical activities until formal organizations are established at the academic institution. To realize the conduct of statistical activities by Department of Medical Informatics, it needs a team of biostatisticians, data analysts and computer personnel.

We searched literature databases regarding the four Japanese universities that published the highest number of life science papers. The databases used in this study were MEDLINE and EMBASE. As a result, there was a 30% difference in the number of papers among the four universities.

In literature database searching, we show that it is necessary to use plural databases for a more improved search. We also compare the results of a single database search with that of multiple database search in the domain of Japanese life sciences. We searched the MEDLINE and EMBASE using the same search terms. There were some differences in the results, owing to differences in the journals and recording methods. We herein show some of the differences in the journals contained in both databases. Furthermore, we show the differences in the number of papers derived from the same journal. Next, as an example of a practical search, we selected some universities in Japan, searched both databases regarding papers published from these universities and then merged the results by hand. According to our results, only 63% of all papers were common to both databases.

We have developed a visual field quantification system that can accurately quantify the measurement results by the Goldmann Perimeter (GP). This system calculates the plural indexes introduced in published papers. In recent years, several isopter quantification methods have been proposed. In these methods, the isopters are digitized and the data are input into a computer, after which a computer program evaluates the changes in the isopters quantitatively. However, each program is only able to evaluate private indexes. We have developed a system that quantifies data using multiple methods. This system used five methods that have been introduced in published papers. With this system, a physician can analyze GP data with multiple methods and can diagnose diseases accurately. We have already input about 2500 GP recording papers into the computer by this system. We then calculated the plural indexes, and visualized the temporal changes in the perimetry.

Abnormal expansion of large granular lymphocytes (LGLs) was observed in peripheral blood and bone marrow in a 28-year-old man. He had general lymphadenopathy and splenomegaly. Surface phenotypical analysis of LGLs showed that these LGLs express CD 2, Ia and NKH-1 but not express CD 3, CD 4, CD 8 and Leu 7. Cytochemical analysis of these LGLs revealed positive acid phosphatase and beta-glucuronidase reaction but negative alpha-naphthyl acetate esterase reaction. These LGLs showed very weak NK activity against only MOLT-4 but showed no cytotoxic activity against K 562. An beta-receptor gene rearrangement of human T-cell receptor was not found by Southern blot analysis. Rapid and fetal clinical course with the results of theses analytical studies showed that this case is highly suggestive of acute leukemia of LGLs which is committed to NK cell lineage.