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Coronary artery calcium, quantified by computed tomography scanning, is one of the well-known measures of subclinical atherosclerosis. Coronary artery calcium is considered an end result from the long-term exposure to risk factors. CAC has been shown to improve risk stratification in asymptomatic individuals with intermediate-risk(e.g., an option to facilitate decision making)for primary prevention of atherosclerotic cardiovascular disease in the US/western countries. Coronary artery calcium also represents a surrogate of atherosclerosis burden. However, the lack of evidence regarding issues such as costs or radiation exposure related to measuring coronary artery calcium warrants further studies.

Immunomodulator (thiopurines) and calcineurin inhibitors (cyclosporine, tacrolimus) have been used in IBD treatment. Thiopurines such as azathioprine and 6-mercaptopur- ine are used in steroid refractory and steroid dependent UC patients. They are also concomitant used both in CD and UC with other drugs including anti-TNFa monoclonal Ab mainly as maintenance therapy. Calcineurin inhibitors, cyclosporine and tacrolimus, are used in moderate to severe refractory UC patients. Adverse effects of thiopruine include bone marrow suppression, liver dysfunction, hair loss, and infectious disease. Recently, it was reported that the risk of acute onset leukopenia in thioprine use is associated with NUDT 15 gene variant, especially in Asian population. Renal dysfunction and infectious disease (e. g. pneumocystis) should be concerned in the patientg treated with calcineurin inhibitors.

The causes of IBD (inflammatory bowel disease), ulcerative colitis and Crohn's disease, have not been elucidated. It is thought that the pathogenesis involves genetic predisposition, environmental factors and host immune response to food antigens and microbiota. Most of IBD susceptiblity genes are related to function of immune cells, maintenance of homeostasis of epithelial cells, autophagy, ER stress and so on. These genetic abnormalities may induce abnormal immune response to antigens and intestinal bacteria, which are modified by diet habit and hygiene environment. Recently, the interrelationship between intestinal bacteria and hosts has dramatically been elucidated, and breakdown of the homeostatic mechanisms at the cellular level is revealed to have an important role in the onset of IBD.

Metabolic bone diseases such as osteopenia and osteoporosis increase the risk of bone fracture that negatively affects quality of life of individuals. Patients with inflammatory bowel disease(IBD), including ulcerative colitis(UC)and Crohn's disease(CD), have been shown to be at increased risk of decreased bone mineral density, however frequency of metabolic bone disease in IBD and identified risk factors are varied among reports.

Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), have been considered as a risk of colorectal cancer (CRC). CRC associated with chronic intestinal inflammation has been known as "colitic cancer". Molecular mechanisms for developing of colitic cancer are different from those of sporadic CRC known as adenomacarcinoma sequence. Colitic cancer often involves dysplasia as precancerous lesions. Mutation of p53 gene is often observed not only in colitic cancer but also in dysplasia. Theory of "field cancerization" applies in colitic cancer resulting in several difficulties in clinical management of it such as multifocality and heterochrony.

Recent advance of molecular biology and immunology contributes to the development biologics such as anti-TNFalpha agent in the treatment for inflammatory bowel disease (IBD). Although therapeutic strategy of IBD has not been changed for a long time, success of Infliximab, first anti-TNFalpha agent, now changes therapeutic strategy of IBD dramatically. Top-down strategy has been considered to improve patients' natural history in the therapy for Crohn's disease as well as in rheumatoid arthritis. Infliximab also has been expected as a promising medicine for pediatric Crohn's disease. Furthermore, Infliximab has been approved for the therapy of ulcerative colitis. These tremendous successes of Infliximab have encouraged us to develop other anti-TNF agents and other biologics. In this review, we describe current topics of biologics in IBD treatment and discuss future direction.

Two hundred thirty-one Campylobacter were isolated from acute diarrheic patients between January 2001 and December 2005. We evaluated annual changes in identified species of Campylobacter and their susceptibilities against antibiotics. Campylobacter jejuni (219 strains; 94.8%) and Campylobacter coli (12 strains; 5.2%) were identified to the species. Susceptibilities to four antimicrobial agents, minocycline (MINO), levofloxacin (LVFX), erythromycin (EM) and clindamycin (CLDM) were examined. The resistant rates of four antimicrobial agents in C. coli were significantly higher than that in C. jejuni. The susceptibility of C. jejuni to LVFX was variable, and MICs gave a bimodal distribution. The resistant rate against EM was estimated to be 9.2% in C. jejuni, 66.7% in C. coli. Moreover, young people ranging from 19 to 24 years old were predominant (47.7%) among the Campylobacter enteritis patients.

We studied 316 adults with community-and hospital-acquired bacterial pneumonia admitted from January 1998 to July 2003. Of these, 66 (20.9%) died. Classified by age, none under 70 died, but mortality increased to 22.6% in the 70-79 age group, 31.6% in the 80-89 age group and 24.2% in the group over 90. Mortality was 3.4% (6/177) for mild pneumonia, 32.0% (24/75) for moderate pneumonia, and 56.3% (36/64) for severe pneumonia. Mortality in hospital-acquired pneumonia (69.1%) was significantly higher than that in community-acquired pneumonia (10.7%). This may result from the higher percentage of moderate by and severe by ill patients who contracted hospital-acquired pneumonia, since 80% of those with hospital-acquired pneumonia were in the moderate and severe group compared to 36.4% of those with community-acquired pneumonia. For antibiotic regimens, mortality was 18.2% to 36.4% for patients who underwent Penicillins-Cephems therapy compared with 51.6% to 66.7% for Carbapenems-Quinolones therapy. The reasons for these differences remain unclear. Our study indicates that severity of illness, age, and antibiotic therapy were factors correlated with death from pneumonia. Underlying diseases such as respiratory failure, chronic heart failure, cerebrovascular disease, renal failure, malignancy, and senile dementia may also be associated with mortality.

The patient was a 50-year-old woman who suffered from gastric discomfort. She was first diagnosed as intrahepatic cholangiocarcinoma with hepatic, paraaortic lymphnodal and bone metastasis. Initial systemic chemotherapy using gemcitabine (GEM) and 5-FU failed to control the disease activity. Then she was given GEM and cisplatin (CDDP) combination chemotherapy. The response was assessed as stable disease (SD), but grade 4 leukopenia was seen. Then systemic therapy using GEM, and hepatic arterial infusion therapy with CDDP, l-leucovorin and 5-FU were continued biweekly. Partial response (PR) was achieved six months later, and her disease status was maintained as SD. This hepatic arterial infusion chemotherapy would be safe and feasible as therapy for inoperable intrahepatic cholangiocarcinoma.

Ulcerative colitis (UC) has been known as inflammatory bowel disease. Progress in UC management strategies has led to optimized approaches for achieving the two primary clinical goals of therapy: induction and maintenance of remission. We here review about immunosuppressants in management of UC; Cyclosporine A (CsA) has been used for the induction therapy in steroid resistant refractory UC. Although it has been reported that CsA has high response rate in severe UC, long-term efficacy (maintenance of remission) has not been proven. To improve maintenance therapy, immunosuppressant has been re-considered in management of UC. In recent years, it has been reported that efficacy of 6-mercaptopurine/azathioprine in maintenance of remission of UC is superior to 5-aminosalicylate (5-ASA). Pharmacological studies have indicated thiopurine methyltransferase (TPMT) activity is essential for maintenance of blood concentration of 6-thioguanine nucleotide (6-TG).

A 50-year-old male with left cervical lymphadenopathy visited our hospital. Infectious and lymphomatous diseases were suspected in the patient. Since the patient owned a dog, which often licked the patient's face, Bartonella infection was also suspected. Histopathological examination in the lymph node biopsy revealed the epithelioid granuloma, but B. henselae was not detected from the culture of the lymphnode. B. henselae DNA also was not detected from the lymph node. Since the antibody titer (lgG) to B. henselae showed 1:128 by immunofluorescent antibody technique (IFA), he was serdogicalg diagnosed as cat-scratch disease. 'Cat-scratch disease' is named after cat scratch, however we propose 'B. henselae infection' which is more appropriate since other animals could serve as a cause of infection.

The efficacy and safety of mesalamine enema were examined in 20 patients with steroid-resistant or dependent, distal ulcerative colitis. Rectal bleeding disappeared in 3 (18%). 8 (50%) of 16 patients within 2 weeks and 4 weeks after the start of mesalamine enema treatment, respectively. Mean clinical activity index (CAI) score after the treatment was significantly reduced (8.1-->3.6, p < 0.001). Furthermore, Mean doses of oral corticosteroid after the treatment (7.3 mg) were also significantly lower than those before the treatment (12.8 mg) (p < 0.01). Four patients dropped out. Three patients could not retain the enemas because of abdominal discomfort and one patient had fever and rash. There were no significant differences in age, gender, disease duration, disease type, and mean doses of oral corticosteroid before the treatment between the response group (n = 8) and the non-response group (n = 8). However, clinical and endoscopic activities before mesalamine enema treatment in the non-response group (CAI 9.8, Matts score 8.0) were higher than those in the response group (CAI 6.4, Matts score 5.5). These results suggest that mesalamine enema is useful for mildly to moderately active distal ulcerative colitis by improving clinical symptoms and reducing corticosteroid.

A 67-year-old man was admitted to our hospital because of advanced gastric cancer associated with metastases to the liver, the lymph nodes along the lesser curvature and the infradiaphragmatic lymph nodes. As we considered the primary lesion and the liver metastases to be unresectable, we treated him with combination therapy of systemic and hepatic arterial infusion chemotherapy. The regimen of systemic chemotherapy consisted of cisplatin (CDDP) and UFT. Hepatic arterial infusion chemotherapy included 5-fluorouracil (5-FU), doxorubicin (DXR) and mitomycin C (MMC). We repeated this therapy six times. The size of the primary lesion and the lymph node metastases decreased significantly after the chemotherapy. The size of the liver metastases did not change, but they appeared to necrotize. The patient maintained a good quality of life during the therapy. He finally died of peritonitis carcinomatosa 18 months after the diagnosis. This case indicated that combination therapy of systemic and hepatic arterial infusion chemotherapy was effective in cases of unresectable gastric cancer associated with liver metastases.

We studied the relationship between DNA index, numerical abberation of chromosome 17 and alterations of the p53 gene in 23 non-small cell lung cancers. Diploid and aneuploid cells from 23 non-small cell lung cancer with DNA aneuploidy were flow sorted into each cell population using FACStar(plus). They were examined by PCR-SSCP analysis for p53 mutation and by microsatellite analysis for loss of heterozygosity at TP53 locus (17p13.1). They were also analyzed by FISH for copy number of chromosome 17. p53 mutations were found in aneuploid cells from the 11 cases (48%). Among them, 8 cases were informative at TP53 locus, and all showed loss of heterozygosity. Aneuploid cells from 16 cases exhibited gain of chromosome 17 copy number in FISH analysis. DNA index was significantly associated with th mean copy number of chromosome 17, suggesting that the number of chromosome 17 changed with DNA index. There were no associations between p53 mutation and DNA index or mean copy number of chromosome 17. In some cases, we also analyzed structural abberation of short arm of chromosome 17 by FISH using p53-cosmid (17p13.1) and Distal 17p (17p13.3-ptel) probes. The p53 gene located on the increased chromosome 17 was lost due to point mutation or deletion of 17p.

We have established anti-colon antibodies producing B cell clones from the patient with ulcerative colitis, and analyzed the immunoglobulin heavy chain variable region (VH) gene segments of these clones using RT-PCR with VH family specific primers. VH3 family was used by all ten clones from ulcerative colitis that produced anti-colon antibodies, while various VH gene families were used by eight clones from normal controls. By nucleotide sequence analysis, two LPL clones were thought to be derived from a germ line gene segment, VH26. However, other three PBL clones were derived from 22-2B, 9-1 and 1.9-III, respectively. These results suggest the heterogeneity of the colonic antigens that autoantibodies in ulcerative colitis recognize.