Serum lipoprotein(a) concentrations are related to coronary disease progression without new myocardial infarction.

OBJECTIVE--To examine the association between serum lipoprotein(a) and angiographically assessed coronary artery disease progression without new myocardial infarction. PATIENTS AND DESIGN--85 patients with coronary artery disease who underwent serial angiography with an interval of at least two years were studied. Progression of coronary artery disease was defined as an increase in diameter stenosis of 15% or more. Vessels on which angioplasty had been performed were excluded from the analysis. The patients were classified into two groups: a progression group without new myocardial infarction (n = 48) and non-progression group (n = 37). Risk factors including lipoprotein(a) were evaluated to see how they were related to progression without myocardial infarction. RESULTS--There were no differences between the two groups in the following factors: age, gender, the time interval between the angiographic studies, the distribution of the analysed coronary arteries, and history of well established coronary risk factors. Univariate analysis showed that serum lipoprotein(a) (P = 0.0002), cigarette smoking between the studies (P = 0.002), serum high density lipoprotein (P = 0.003), and serum low density lipoprotein (P = 0.01) were related to progression without myocardial infarction. Multivariate analysis selected two independent factors for progression without myocardial infarction: serum lipoprotein(a) (P = 0.003) and serum high density lipoprotein (P = 0.03). CONCLUSIONS--Serum lipoprotein(a) concentrations are closely related to the progression of coronary artery disease without new myocardial infarction. Lipoprotein(a) lowering treatment may be needed to prevent disease progression in patients with coronary artery disease and high serum lipoprotein(a).     

Identification of hepatitis C virus 1b-derived peptides recognized by both cellular and humoral immune systems in HCV1b(+) HLA-A24(+) patients.

Despite scientific advances, the therapeutic options for hepatitis C virus (HCV) are limited by poor response rates. HCV1b is particularly resistant to standard interferon therapy. The inhibition of the progression of chronic hepatitis and liver cirrhosis and the prevention of the occurrence and recurrence of hepatocellular carcinoma (HCC) are important and thus, there is a need for new therapeutic modalities for HCV1b infection. We, therefore, investigated highly immunogenic peptides and report in this study three novel candidate peptides (at positions 711-720 in envelope 2 protein, 885-893 in non-structural protein 2 and 1716-1724 in non-structural protein 4B) among 35 peptides of conserved regions of HCV1b proteins containing HLA-A24 binding motifs tested. Namely, HCV(711-720), HCV(885-893) and HCV(1716-1724) induced HLA-A24-restricted and peptide-specific cytotoxic T lymphocytes (CTLs) activity in peripheral blood mononuclear cells (PBMCs) from 7, 6 and 5 of 12 patients and also were recognized by plasma of 8, 5 and 7 of 12 HCV1b(+) patients, respectively. These results may provide new insight into the development of a peptide-based specific immunotherapy for HCV1b(+) HLA-A24(+) patients.     

Experimental gastric carcinogenesis related to Helicobacter pylori

In this paper, we present our research on the lipid A of Helicobacter pylori, an experimental study using the Mongolian gerbil model and experimental carcinogenesis using the mouse model to evaluate roles of host factors and bacterial factors which are related to the pathogenicity of Helicobacter pylori including gastric carcinogenesis. Future study on bacterial factors and host factors may give more insight into the role of Helicobacter pylori in gastric carcinogenesis.     

Successfully treated unstable angina pectoris in a young Japanese female

A 25-year-old Japanese female complaining chest oppression and palpitation was admitted to hospital under the presumptive diagnosis of ischemic heart disease (IHD), although no obvious underlying disease associated with IHD was detected. Coronary angiography showed stenosis at the proximal site of left anterior descending artery (LAD), with dilatation and tortuosity at the bifurcation of the first and the second septal branches. Intravascular ultrasound imaging of the LAD showed intimal thickness without calcification at the site of stenosis. The stenosis was successfully and smoothly dilated by percutaneous transluminal angioplasty. Even with precise evaluation, the cause of the coronary artery disease in this young female patient was not clarified. Further careful follow-up is needed.     

Defense mechanisms against influenza virus infection in the respiratory tract mucosa

The respiratory tract mucosa is not only the site of infection for influenza viruses but also the site of defense against virus infection. Viruses are initially detected and destroyed non-specifically by innate immune mechanisms, but if the viruses escape the early defense mechanisms, they are detected and eliminated specifically by adaptive immune mechanisms. The major adaptive immune mechanisms are as follows. (i) Specific secretory-IgA (S-IgA) antibodies (Abs) and CTLs (CD8+ cytotoxic T lymphocytes) are involved in the recovery from influenza following viral infection of naive mice. (ii) Preexisting specific S-IgA and IgG Abs in the immunized animals are involved in viral elimination by forming virus-Ig complexes shortly after re-infection. By their polymeric nature, the S-IgA Abs, which are carried to the mucus by transepithelial transport used for dimeric IgA (dIgA) Abs, provide not only protection against homologous virus infection but also cross-protection against drift virus infection. The IgG Abs, which transude from the serum to the mucus by diffusion, provide protection against homologous virus infection. They are largely distributed on the alveolar epithelia to prevent influenza pneumonia. (iii) In the absence of Abs in the pre-immunized animals, the production of specific IgA and IgG Abs by B memory cells is accelerated after re-infection, and these antibodies play a role in viral elimination from day 3 onwards after re-infection. (iv) In epithelial cells of infected animals, specific dIgA Abs being trafficked through the epithelial cells may be involved in the prevention of viral assembly by binding to newly synthesized viral proteins. (v) In the pre-immunized animals, CTL production by memory T cells is also accelerated and these cells appear to participate in the killing of the host cells infected with different subtype viruses (within the same type) from day 3 onwards after re-infection. (vi) Similarly, memory Th1 cells that mediate an accelerated delayed-type hypersensitivity response are involved in blockade of virus replication by secreting IFN-gamma in mice challenged with different subtype viruses. These defense mechanisms suggest that the development of a mucosal vaccine, capable of inducing S-IgA Abs, which provide cross-protection against variant viruses within the same subtype, serum IgG Abs to prevent lethal influenza pneumonia and CTLs, which provide broad cross-protection against different subtype viruses, is strategically important to control influenza.     

Ultrasonography of gastric volvulus: "peanut sign"

We report a case of chronic gastric volvulus in which ultrasonography (US) was useful. An 81-year-old woman was hospitalized due to vomiting, and upper gastroduodenoscopy revealed that the stomach was spirally twisted and constricted. An upper gastrointestinal barium study demonstrated an organoaxial-mesenteroaxial combined type gastric volvulus. US showed constriction between the dilated upper stomach body and the lower stomach body similar to a "peanut". Thereafter, the patient's vomiting stopped and follow-up US demonstrated that the constriction of the stomach was loosened. Therefore, we believe that this characteristic US sign paralleled the symptoms of the patient.     

Liver disease in hepatitis C virus carriers identified at blood donation and their outcomes with or without interferon treatment: Study on 1019 carriers followed for 5–10 years

Aim: To portray liver disease and project outcomes in carriers of hepatitis C virus (HCV) in the general population. Methods: Liver disease was evaluated in 1019 individuals who were found with HCV infection at blood donation, and they were followed for 5-10 years with or without receiving interferon (IFN). Results: At baseline, chronic hepatitis was detected in 529 (51.9%) HCV carriers and more frequently in men than in women (62.6% [299/478]vs 42.5% [230/541], P < 0.01); cirrhosis was diagnosed in five (0.5% [three men included]) and hepatocellular carcinoma (HCC) in one (0.1% [man]). Of the carriers who were followed for 5 years or longer, loss of HCV-RNA from serum was achieved in 61 (31.0%) of the 197 treated with interferon (IFN) and only one of the 211 (0.5%) without IFN (P < 0.0001). HCC developed in 14 carriers including six ofthe 211 (2.8%) without IFN and eight of the 197 (4.1%) with IFN (six non-responders included). Follow ups of the 949 carriers identified age (P < 0.002), male gender (P < 0.01) and cirrhosis at the baseline (P < 0.0001) as factors contributing to the development of HCC. Cumulative incidence rates of HCC during 10 years among carriers found with chronic hepatitis increased in parallel with the age at the baseline. Conclusion: Identification of HCV carriers in the general population and treating those indicated with IFN would help decrease the development of HCC and lift its medical, as well as economic, burdens off society.     

Recombinant interferon-α-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study

Abstract: To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-α-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-α-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p=0.64). In addition, there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group (26%) and 6-MU group (29%). Multivariate stepwise regression analysis revealed that serum HCV-RNA level (p=0.0035) and platelet count (p=0.0009) were independent variables useful in predicting a sustained response of ALT. The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10⁵ copies/ml and serum platelet level above 15×10⁴/μl was 71%, whereas that in patients with a serum HCV-RNA level above 10⁵ copies/ml and serum platelet level less than 15×10⁴/μl was 12%. These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets, even if treated with a low dose of IFN.