Cigarette smoking and subsequent risk of lung cancer by histologic type in middle-aged Japanese men and women: the JPHC study

In order to update the findings of relative risk associated with cigarette smoking for lung cancer by histologic type in Japan, the data from a population-based cohort study of 91,738 men and women were analyzed. During 1990-1999, 422 lung cancer incident cases were identified. The relative risk for all incident cases associated with current smokers versus non-smokers was 4.5 [95% confidence interval (CI): 3.0-6.8] and 4.2 (95% CI: 2.4-7.2), for men and women, respectively. When divided by histologic type, relative risk for squamous cell carcinoma and small cell carcinoma was 12.7 (95% CI: 4.7-34.7) and 17.5 (95% CI: 4.9-62.1), while for adenocarcinoma it was 2.8 (95% CI: 1.6-4.9) and 2.0 (95% CI: 0.8-5.0) for men and women, respectively. We confirmed that the lung cancer risk in men rose with increasing cigarette smoking, especially the duration of smoking among current smokers and decreased after the cessation of smoking among former smokers. Unlike the US or European countries, the relative risk did not increase in this updated study, compared with previous studies in 1960s to 1990s in Japan either for all incident cases or for specific histologic types and the magnitude of relative risks was substantially lower than that observed in the US or European countries, especially for adenocarcinoma.     

Expression of tissue factor is associated with clinical features and angiogenesis in prostate cancer

BACKGROUND: Tissue factor (TF), the main initiator of blood coagulation, is involved in cancer metastasis and progression. We examined the role of TF on prostate cancer. MATERIALS AND METHODS: Immunohistochemical analysis was performed using the anti-TF antibody. Intra-tumoral blood vessels were visualized by staining endothelial cells with CD34 antibody. We examined the expression of TF and the microvessel density (MVD) in 66 biopsy specimens of prostate cancer, in order to investigate the relationship between the expression of TF and the clinicopathology of prostate cancer. RESULTS: TF antigen was positive in 41 (62%) of the specimens. There were significant differences in TF expression according to the pretreatment prostate specific antigen (PSA) level (p = 0.0193) and bone metastasis (p = 0.0029). MVD was significantly related to bone metastasis (p = 0.0175). TF-positive carcinomas more frequently presented high MVD expressions (p = 0.017) than TF-negative tumors. CONCLUSION: These results suggest that increased angiogenesis associated with TF expression might cause the metastasis and progression of prostate cancer.     

CD19 expression and growth inhibition of tumours in human multiple myeloma

Multiple myeloma (MM) is a proliferative disorder of monoclonal plasma cells which accumulate in human bone marrow (BM). CD19 is a hallmark differentiation antigen of the B cell lineage and positively regulates antigen receptor signal transduction in mature B cells. We have previously shown that malignant plasma cells (myeloma cells) isolated from the MM patients lack the CD19 expression, while non-malignant plasma cells isolated from the healthy donors do express the CD19 antigens. It is also intriguing that there exists both CD19- and CD19+ plasma cells in some cases in pre-myeloma states including monoclonal gammopathy of undetermined significance (MGUS). It indicates that MGUS is usually composed of phenotypically non-malignant (CD19+) and malignant (CD19-) plasma cells. Furthermore, we recently demonstrate that, expression of the CD19 gene markedly inhibits the proliferation of human myeloma cell lines in vitro, and exhibits the reduced tumorigenicity in vivo and no anchorage-independent growth in vitro of a tumorigenic myeloma cell line. This inhibitory effect might result from the CD19-mediated intracellular signals because it is not observed in cells expressing the mutant CD19, which lacks the cytoplasmic domain. In this review, we suggest that loss of CD19 in MM could contribute to the proliferative advantage of the malignant plasma cell clones in this disease. Furthermore, we propose the usefulness of the phenotypic analysis of plasma cells in human plasma cell dyscrasia as a new diagnostic tool, and the CD19 gene as a potential target for the gene therapy in MM.     

Significance of peritonectomy for peritonitis carcinomatosis

We analyzed patients who underwent multimodal treatment with peritonectomy as an aggressive treatment for peritonitis carcinomatosis. Peritonectomy was treated in eighteen cases (eleven gastric cancer, seven colon cancer). Out of these eighteen cases, nine were initial operation, six were recurrence after first operation and three were for relief after palliative operation for peritoneal dissemination. Five cases of recurrence included ileus. Of all eighteen patients, ten had received preoperative chemotherapies. Peritonectomy made complete resection possible principle, and the procedure included resection of the primary lesion, subtotal colectomy and peritonectomy. An intestinal stoma was needed in nine cases, consequently. All patients cases underwent continuous hyperthermic peritoneal perfusion (CHPP). Early postoperative peritoneal chemotherapy was given in five cases. By peritonectomy for a first time operation, macroscopically complete resection was possible in six cases. In relief and recurrence cases few tumor cells remained in five cases. Ileus due to peritoneal carcinomatosia was eliminated in all cases, and caloric intake became possible. Fourteen cases had postoperative complication (morbidity 78%), and treatment-related death occurred in three cases (mortality 17%). It became possible to resect even the peritoneal dissemination that was inoperable by conventional surgery, and improvement of QOL was achieved by peritonectomy in cases of carcinomatous peritonitis. However, postoperative care is important since aggression becomes more intense.     

Case report of meningoencephalitis during a concomitant mumps and parvovirus B19 infection

A 19-year-old, immunologically healthy man suffered from prolonged and intermittent high fever, left parotitis, systemic lymph node swelling, progressive liver dysfunction and leukocytopenia. 11 days after the fever onset, consciousness disturbance and generalized convulsion occurred. By the administration of γ-globulin and steroid, the patient recovered completely. Serum titers of IgG and IgM specific for both human parvovirus B19 and mumps were elevated, and parvovirus B19 DNA was identified in the serum. It was speculated that overlap infection of mumps and parvovirus B19 made the disease more severe in this patient.     

HLA-A2-restricted cytotoxic T lymphocyte activity during interferon beta therapy in patients with chronic hepatitis C

BACKGROUND AND AIMS: Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) may contribute to viral clearance and liver cell injury in patients with chronic hepatitis C. In the present study, we attempted to determine the serial HCV-specific CTL activity during interferon-beta (IFN-beta) therapy in patients with chronic hepatitis C and whether there is any relationship between the CTL response and clinical response to IFN-beta therapy. METHODS: Eight HLA-A2-positive patients with chronic hepatitis C were treated initially with 6 million U/ml of IFN-beta every day for 8 weeks and then 3 times weekly for the subsequent 16 weeks. Peripheral blood mononuclear cells (PBMC) were collected before the start, 4 weeks after the start, and after the end of IFN treatment and were stimulated with 2 peptides corresponding to core sequences, which were previously reported to have an HLA-A2 restricted-CTL epitopes. Cytolytic activity was determined by a standard 51Cr-release assay using allogenic HLA-matched EBV-transformed B lymphoblastoid cell lines (B-LCL). RESULTS: HCV-specific CTL responses were detected in 2 of the 8 patients before treatment with IFN-beta. One of 2 patients was not observed HCV-specific CTL responses after 4 weeks of IFN-beta treatment, however these two patients showed CTL responses at the end of IFN-beta treatment, and finally HCV-RNA was negative. In addition, HCV-specific CTL responses were observed in 4 patients after 4 weeks of IFN-beta treatment. Three of these 4 patients showed CTL responses only at 4 weeks after IFN-beta treatment. However, there were no differences between clinical parameters or between IFN efficacy in HCV specific CTL response-positive (n = 4) and -negative (n = 4) patients at 4 weeks after the start of IFN-beta treatment. CONCLUSIONS: These findings suggest that there are few relations between peripheral HCV-specific CTL response and clinical response to IFN therapy in patients with chronic hepatitis C, although IFN enhances the host immune response against HCV synergistically with antiviral activities.     

Glucocorticoid-induced osteoporosis: pathogenesis and management

Glucocorticoid- (GC-) induced osteoporosis and an increased risk of fractures are one of the most serious problems for patient using long-term GC therapy, such as those with rheumatoid arthritis, autoimmune diseases, inflammatory bowel diseases, bronchial asthma, and chronic lung diseases. GCs are known to affect both bone formation and resorption. In rheumatoid arthritis, the etiology of bone loss is multifactorial, including local inflammation around joints, release of bone-absorbing cytokines, physical inactivity, and malnutrition, in addition to the use of GC. Two guidelines have been published, by the American College of Rheumatology Task Force in 1966 and by the UK Consensus Group in 1998. Both guidelines recommend that patients receiving GC therapy at doses of 7.5 mg/day of prednisolone or more for 6 months or longer should have their bone mineral density measured and begin preventive therapies. Calcium and vitamin D supplements, sex hormone replacement, and weight-bearing exercise are the first-line therapies. For patients who are unable to take sex hormone replacement therapy (HRT), bisphosphonates are recommended by both guidelines. In this article, we briefly summarize the pathogenesis of GC-induced osteoporosis and its prevention and treatment. Received: April 7, 2000     

Smoking and risk of premature death among middle-aged Japanese: ten-year follow-up of the Japan Public Health Center-based prospective study on cancer and cardiovascular diseases (JPHC Study) cohort I.

To update the evidence on the association between smoking and mortality, we analyzed data from a population-based prospective study in Japan. In total, 19950 men and 21534 women aged 40 - 59 who reported their smoking history and had no serious disease at baseline survey were followed. During 1990 - 1999, 1014 men and 500 women died. Smokers were associated with an unhealthy lifestyle. Relative risks (RRs) for selected cause of death due to smoking were slightly attenuated by adjusting for possible confounding factors. Age- and area-adjusted RRs of male current smokers compared with never smokers were 1.66 (95% confidence intervals (CI): 1.40, 1.95) for all causes, 1.69 (1.31, 2.18) for all cancers, 1.67 (1.20, 2.34) for all circulatory system disease, and 1.63 (1.24, 2.15) for other causes, while those of females were 2.03 (1.52, 2.73), 2.06 (1.35, 3.15), 2.99 (1.75, 5.11), 1.31 (0.69, 2.51), respectively. After adjusting for multivariate variables, the corresponding RRs of male smokers were 1.55 (1.29, 1.86), 1.61 (1.20, 2.15), 1.41 (0.97, 2.03), and 1.61 (1.17, 2.19), against 1.89 (1.36, 2.62), 1.83 (1.14, 2.95), 2.72 (1.45, 5.07), and 1.39 (0.71, 2.73) for females. Twenty-two percent of death from all causes, 25% of all cancer, and 17% of all circulatory system disease deaths, could be attributed to cigarette smoking in males, and 5%, 4%, and 11% in females, respectively. Cumulative dose as indicated by pack-years was clearly associated with cancer death. These findings provided information as to the quantitative risk for premature death due to smoking among middle-aged Japanese men and women, and showed that the elevated risk was not explained by the unhealthy lifestyle of smokers.     

Conditions That May Determine Blood Vessel Phenotype in Tissues Grafted to Brain

The hypothesis, that a blood vessel's phenotype is determined by the tissue it vascularizes and not by the vessel's source, does not hold for tissue beyond a certain period of development. In mature skeletal muscle grafted to choroid plexus of adult and 2-week-old rats, some vessels were choroidal or fenestrated (FV) rather than, according to the hypothesis, continuous (CV), like those of muscle. In E14 fetal muscle placed on the choroid plexus, 80% of the grafts' capillaries were CV, like those of muscle. Most choroidal FV that entered the grafts were apparently changed to CV. By E16, about 70% of the graft vessels remained as FV rather than being converted. Thus, FV were changed to CV by a hypothetical conversion factor made, apparently, by E14 grafts but not by E16 grafts. In grafts from [³H]thymidine-labeled donors, an appreciable number of CV in E14 grafts were identified as intrinsic to the muscle. When hosts were labeled to verify the origin of FV in their nonlabeled donor grafts, only a few FV, to date, were tagged. The FV must have come from host choroid plexus, the only available source of graft FV. Vascular endothelial growth factor (VEGF) might convert CV into FV, yet VEGF and the mRNA for its receptor were present in choroid plexus but not in the grafts. Therefore, VEGF is not a conversion factor. The purported factor that changes FV to CV may be expressed in E14 muscle grafts but diminishes by fetal age E16 and beyond.