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It has been reported that tumor cell-intrinsic cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING) pathway is essential for radiotherapy(RT)-induced activation of anti-tumor immune responses. However, its role in the RT- induced remodeling of the tumor microenvironment(TME)in esophageal squamous cell carcinoma(ESCC), is largely unknown. In this study, we found that the tumor cell-intrinsic cGAS-STING pathway is a critical component for RT-induced activation of immune cells in the TME through the induction of type Ⅰ interferon and C-X-C motif chemokine ligand 10 in tumor cells in ESCC. However, at the same time, the tumor cell-intrinsic cGAS-STING pathway is also involved in RT-triggered infiltration and polarization of immunosuppressive CD163+ tumor-associated macrophages (TAM) through the induction of interleukin 34 (IL-34) in tumor cells in ESCC. Our findings suggest that targeting IL-34 to impede the infiltration and polarization of CD163+ TAM could potentially enhance the efficacy of RT-induced immune cell activation in ESCC TME.

Deficient mismatch repair (dMMR)/microsatellite instability (MSI)-H colorectal cancer (CRC) has high immunogenicity. Although the cyclic GMP-AMP synthase( cGAS)-stimulator of interferon genes( STING) pathway activation has considerably contributed to the high number of CD8+ tumor-infiltrating lymphocytes (TILs), its role in dMMR/MSI-H CRC is largely unknown. In this study, we investigated the association between cGAS-STING expression and CD8+ TILs in CRC. Data analysis using the TCGA dataset CRC cohort showed that cGAS, STING, and CD8 gene expression levels were significantly higher in the MSI group. Immunohistochemistry examination of resected clinical CRC samples showed that cGAS-STING expression in tumor cells was high in the MSI CRC, and CD8+ TILs was also significantly infiltrated in the MSI group. Moreover, significant CD8+ TILs infiltration was observed in CRC with high cGAS and STING expression levels. The results suggest that dMMR/MSI -H CRC has maintained a high cGAS-STING expression, which may contribute to abundant CD8+ TILs.

Despite the remarkable progress in cancer therapy, the 5-year survival rate for esophageal cancer patients who can be treated with surgery is still limited to 59.3%. We have recently treated patients with advanced or recurrent esophageal cancer with anti-PD-1 antibody as a new treatment strategy. However, its response rate was not as high as expected at 19.3%, and the development of new therapeutic strategy to further improve its efficacy is eagerly expected. In this study, we investigated the possibility of combinatorial cancer immunotherapy using anti-PD-1 therapy and local radiotherapy in order to enhance the therapeutic efficacy of anti-PD-1 therapy. As a result, although chemoradiotherapy induced the tumor antigen specific cytotoxic T lymphocytes(CTL)in about 40% of patients with advanced esophageal squamous cell carcinoma (ESCC), PD-L1 expression on ESCC cells was observed in approximately 80% of ESCC patients. This means that induced tumor antigen specific CTL may be immunosuppressed through the PD-1 pathway at the ESCC tumor microenvironment, and the addition of anti-PD-1 therapy could be effective in such a situation. Although further studies are needed, the combinatorial cancer immunotherapy using anti-PD-1 therapy and local radiotherapy is expected to be a promising treatment strategy in patients with ESCC.

The Tn antigen is the most prevalent tumor-associated carbohydrate antigen. It interacts with macrophage galactose-specific lectin(MGL)on dendric cells and macrophages, driving immune inhibitory signals. Colorectal cancer(CRC)exhibiting deficient mismatch repair(dMMR)is characterized by tumor-infiltrating lymphocytes(TILs), the expression of immune checkpoint molecules, and immune evasion. We recently reported that Tn antigen expression was associated with dMMR and that dMMR CRCs with strong Tn antigen expression demonstrated CD8+ T cell exclusion and a lack of PD-L1 expression. Our findings suggest that the immune cold subset of dMMR CRCs with strong Tn antigen may be effectively treated with immune checkpoint blockade therapy or cellular immunotherapy targeting Tn antigens.

Cancer immunotherapy, which is attracting attention as a fourth treatment strategy for cancer therapy, eliminates cancer cells using own immune system. Therefore, the state of tumor immune responses is very important to elicit the efficacy of cancer immunotherapy. Recently, the association between the efficacy of cancer immunotherapy using immune checkpoint inhibitors and certain intestinal bacteria has been reported. It is suggested that certain intestinal bacteria may regulate tumor immune responses. We also reported that intestinal bacteria such as Bifidobacterium, Bacteroides, and Faecalibacterium (genus level)were increased in patients with high frequency of infiltrating effector regulatory T cells in the tumor microenvironment of advanced colorectal cancer. In this article, we presented the association between intestinal bacteria and tumor infiltrating immune cells, such as regulatory T cells and tumor associated macrophages, in the tumor microenvironment of advanced colorectal cancer, focusing on results of our research. Subsequently, we introduced the possibility of clinical application of intestinal bacteria based on the review of reported articles.

The patient was a 66-year-old male who had undergone an operation for lung cancer and solitary brain metastases. Follow- up PET-CT after 1 year detected FDG accumulation in the stomach. We performed esophagogastroscopy and found an approximately 20 mm-sized Type 2 tumor on the greater curvature of the upper stomach. A pathological diagnosis of lung adenocarcinoma metastasis in the stomach was made. Laparoscopic surgery was performed on the metastatic lesion to prevent bleeding and perforation, and resection was achieved with minimal invasion. The current development of chemotherapy, including immunotherapy, has contributed to the improved prognosis of cancer patients, including those with lung metastasis in the stomach. Considering these backgrounds, preventive surgical resection under laparoscopy may be an effective approach for improving prognosis and preventing acute life-threatening adverse events. We report this case along with a literature review.

Spontaneous spinal epidural hematomas(SSEH)are rare. The causes of SSEH include hematologic disorders, anticoagulation and antiplatelet therapy, vascular malformations, neoplasms, trauma, or medical interventions, such as epidural catheterization or spinal surgery. However, the cause is usually unclear in most cases. We report a case of SSEH during chemotherapy with paclitaxel and ramucirumab for advanced gastric cancer. A 68-year-old woman was referred to our hospital with a diagnosis of advanced gastric cancer. After 4 courses of neoadjuvant chemotherapy containing S-1 plus oxaliplatin, distal gastrectomy with D2 lymphadenectomy was performed. Postoperative chemotherapy with paclitaxel and ramucirumab was initiated, with a diagnosis of ypStage Ⅲc(T4aN3bM0). She was later transported by ambulance to our hospital with symptoms of sudden onset posterior neck pain and weakness of the extremities. Magnetic resonance imaging(MRI)of her cervical spine showed an epidural hematoma from C2 to C5. The symptoms improved gradually after admission, and the epidural hematoma decreased in size on MRI. Hemorrhagic events such as SSEH should be considered during treatment with angiogenesis inhibitors.

Recently, immune checkpoint inhibitors(ICI)has been developed rapidly as a novel cancer therapy. In particular, the number of worldwide clinical trials using anti-PD-1/anti-PD-L1monoclonal antibodies(mAb)are ongoing in various types of cancer. On the other hands, the response rate of anti-PD-1/anti-PD-L1 mAb monotherapy has been around 10-40% in various types of cancer, therefore, the development of biomarker for them are urgently needed. The following conditions in the tumor microenvironment are necessary for anti-PD-1/anti-PD-L1mAb therapy; the coexpression of HLA class Ⅰand PDL1 on tumor cells, and the existence of CTL around tumor cells. In this review, we discussed the mechanism of PD-L1 expres- sion and the development of biomarker of anti-PD-1/anti-PD-L1 mAb from the viewpoint of IFN-γ that can induce those conditions in the tumor microenvironment.

A 73-year-old woman noticed a mass in her right breast about 1 year ago and consulted our hospital for an enlarged mass of about 10 cm in diameter.She was diagnosed with locally advanced triple negative breast cancer, and we initiated S-1 treatment as neoadjuvant chemotherapy.After 4 chemotherapy courses, computed tomography showed that the primary tumor had shrunk.Therefore, right mastectomy and axillary dissection were performed, and UFT was administered after surgery.She is currently alive with no recurrence 18 months after surgery.

The response rate of anti-PD-1/anti-PD-L1antibody alone is about 20 to 30%and the development of biomarker for them is important to know their indication. Based on previous reports and our research results, we suggested that basic candidates of biomarker for anti-PD-1/anti-PD-L1antibody are the expression of PD-L1and HLA class I on cancer cells and the invasion of CD8 positive T cells in tumor microenvironment. Furthermore, in addition to these conditions, regulatory T cells and immune cells expressing PD-L1in tumor microenvironment, and microsatellite instability of cancer cells will be considered in the future.

Programmed cell death 1(PD-1)/PD-ligand 1(PD-L1)immune checkpoint blockade has emerged as a promising therapeutic strategy in various types of cancer. In a recent phase II clinical trial, treatment with the anti-PD-1 agent, pembrolizumab, resulted in considerable clinical benefit in patients with mismatch repair(MMR)-deficient colorectal cancer(CRC). Upregulation of PD-1on T-cells and PD-L1 on tumor cells induces inhibitory signals to suppress T-cell activation, leading to an immune-suppressive microenvironment particularly in MMR-deficient tumors. However, the regulation of PD-L1 expression on CRC cells is poorly understood. We hypothesized that certain microRNAs(miRNAs)are involved in the immunosuppressive microenvironment by directly targeting PD-L1. We identified candidate miRNAs by RNA-sequence analyses for mRNA and miRNA expression obtained from the TCGA colon adenocarcinoma database combined with miRNA target prediction programs. We found that forced miRNA expression could decrease PD-L1 expression on cancer cell lines. Our findings may facilitate an understanding of the role of miRNAs in PD-L1 regulation and also suggest potential miRNAs to serve as biomarkers and therapeutic targets for cancer immunotherapy.

Therapeutic cancer vaccine enhances a specific immune response against tumor cells in vivo, resulting in exertion of antitumor effects. On the other hand, immune checkpoint inhibitors promote the induction of tumor-specific T cells and also enhance the cytotoxic abilityof these T cells in tumor microenvironment. There is a possibilitythat immune checkpoint inhibitors enhance tumor immune responses induced bytherapeutic cancer vaccine, and it is expected that additive or synergistic effects will be obtained bythe combination of them. Moreover, according to previous reports, we should use an immune checkpoint inhibitor to enhance the cytotoxic ability of tumor-specific T cells as the combination for therapeutic cancer vaccine. Furthermore, the combination of a specific antibodyagainst newlyidentified co-inhibitoryreceptors (Lag-3, Tim-3, TIGIT, etc)and a therapeutic cancer vaccine is also one of newlyexpected treatments in the future.

In recent years, Japan has been hit by natural disasters such as earthquakes, typhoons, torrential rains, and heavy snow every year without exception. When such disasters occur, human lives are put at risk. These emergency situations are an unrivaled sphere of activity for physicians, nurses, and emergency life-saving technicians, and the need for these workers becomes the focus of society; however, for advanced rescue in the acute phase of disasters and to prevent disease onset in the chronic phase, clinical laboratory tests are expected to play a major role in developing more accurate diagnoses and promoting prompt medical care. In this paper, I examine whether clinical laboratory tests are beneficial for practicing disaster medicine.

HLA class I and PD-L1expressed on cancer cells play a pivotal role in the CTL recognition mechanism against cancer cells in the tumor microenvironment. It is well known that IFN-g upregulates PD-L1as well as HLA class I expression in cancer cells, and it is suggested that TILs, including CTL, produce IFN-g in the tumor microenvironment. Therefore, there is a possibility that IFN-g produced by activated TILs upregulate both HLA class I and PD-L1expression in cancer cells in the tumor microenvironment. We propose that the anti-tumor effect of CTL could be enhanced if the inhibition of CTL recognition mechanism against cancer cells via the PD-1/PD-L1pathway is canceled by anti-PD-1or anti-PD-L1antibody.

The three types of certifying examinations provided by the College of Laboratory Medicine of Japan are introduced. They are the Technologist in Laboratory, Specialist in Laboratory, and Technologist in Emer- gency Laboratory. Both the Technologist in Laboratory and Specialist in Laboratory examinations focus on eight areas: microbiology, pathology, chemistry, hematology, immunology, cardiology, neurology, and respi- rology. The Technologist in Laboratory examination started in 1954, and, as of today, it has been passed by 34,646 people. The Specialist in Laboratory examination started in 1956, and due to its level of difficulty, it has been passed by only 232 people. Meanwhile, the Technologist in Emergency Laboratory examination start- ed in 1992, and it has been passed by 5,047 people. These certificates prove that their holders have acquired a certain level of knowledge and technical aptitude, and that they represent the caliber of personnel necessary for clinical laboratories to obtain facility authentication from organizations such as the International Organiza- tion for Standardization (ISO) and the College of American Pathologists (CAP). Therefore, the significance and value of acquiring these qualifications are marked. [Review].

This symposium is named "Required education for medical technologists of the next generation", and is held under the joint sponsorship of the Japanese Association of Medical Technology Education. We received lectures by two speakers from the clinical field and two speakers from a medical technology educational institution. From the perspective of the medical technology education institution, we were introduced to education that is actually being provided. From the clinical perspective, we were given lectures that concretely discussed the necessary role of medical technologists in clinical practice. All of the lectures were very interesting and helpful.

Becoming a Medical Technologist capable of contributing to the clinical field requires an ability to keep up with rapid advances in the field of medicine, as well as the diligence to constantly keep abreast of new discoveries and technologies. To this end, one should forge a social identity as a Medical Technologist, thereby bringing more esteem to the profession. Moreover, applying knowledge of medical laboratory work to not only medicine but also other fields is linked with maintaining and improving public health, which is an important objective for the Medical Technologist. In society, the various certifications held by such Medical Technologists are acquired as part of a lifelong learning process and not only lead to individual advancement but also, presumably, business expansion through the application of prodigious knowledge and skills.

We have developed a multi variate analysis of social communication behavior which allows for discriminating the emotional state of an agent interacting with other agents (Bouquet method). Domestic chick or common marmoset was reared under socially isolated conditions, later tested for its development of communication behavior with peers by Bouquet, and compared with that of animals reared under grouping conditions. We found the existence of high sensitive period for social interaction, given less experience, developing less affiliated behavior. From chick model, a couple of neuronal difference was observed between two groups, amygdale core central cell size, MRI volumetric measure in mesolimbic area, and gene expression patter including brain type tryptophan hydroxylase in nucleus accumbens. The isolated chick behavior changed better to be socially affiliated by taking SSRI/SNRI or Ubiquinol (the reduced form of CoQ10) together with social interaction experience after the sensitive period. Finally, we could discriminate the behavior of Asperger syndrome children (n = 7) from that of the typically developed siblings (n = 6) during the clinical interview by applying Bouquet method.

Although esophageal squamous cell carcinoma (ESCC) patients have recently been treated with the combined modality therapy, the prognosis remains poor. For the development of new strategies in ESCC, we examined possibilities of the immune -based therapy with cytotoxic T lymphocyte (CTL) and the molecular targeting therapy for HER2 against ESCC in this study. At first, we assessed HER2 and MHC class I expression by immunohistochemistry in ESCC patients and analyzed the correlation between them. Subsequently, the effect of molecular targeting therapy for HER2 was evaluated in a panel of ESCC cell lines. According to these results, we suggested that HER2 over-expressing ESCC patients (11.8%) are good candidates for the molecular targeting therapy for HER2 and HER2 negative/low-expressing ESCC patients (88.2%) for the immune-based therapy with CTL. Furthermore, the combination therapy of Herceptin and lapatinib is a new promising strategy for HER2 positive ESCC patients (29.4%).

Now the education of medical technologists has reached the fourth turning point. The first turning point was the start of the two year education in 1958 and the second was the start of the three year education of medical Technologists in 1971 and the third was the start of the full-fledged university education in 2004 and, this time, the fourth turning point is the start of graduate school education of medical technology. From this situation, for education of graduate school, mind education that polishes personality practically is may be demanded, Therefore, human resource development with not only knowledge and technique as medical technologists but also with humanly nurtured sentiment is expected in the future.

A 69-year-old man, who had been followed up for sarcoidosis at another hospital from 10 years previously, was referred to our hospital because of a new lesion in the left upper lobe. A chest CT scan revealed a nodular lesion at the orifice of the left B3b and mediastinal lymphadenopathy. Bronchoscopic biopsy established a diagnosis of squamous cell carcinoma. Because there had been no distant metastasis and no change in size of the mediastinal lymph nodes over the previous 5 years, left upper lobectomy with lymph node dissection was performed. The histology of the resected tumor indicated a moderately-differentiated squamous cell carcinoma, and the dissected lymph nodes contained non-caseous epithelioid cell granuloma without metastasis. Thus, we made a final diagnosis of squamous cell carcinoma (pT1N0M0, stage IA) that complicated the sarcoidosis. Surgical resection can be the first option for lung cancer complicating sarcoidosis with mediastinal lymphadenopathy, because making a preoperative assessment of N status is difficult.

A 77-year-old man underwent radiotherapy for the squamous cell carcinoma of the right lung. Two months after the 60Gy/30fr irradiation was completed, he complained of dyspnea and his chest X-ray showed ground glass opacities and reticular shadows in both lung fields. Severe radiation pneumonitis was diagnosed. Two grams of methylprednisolone did not improve his symptoms and on the next day his hypoxemia worsened. We then tried plasma exchange because of his critical status. His respiratory status improved rapidly after plasma exchange and his chest X-ray showed remarkable improvement 10 days later. We think this case suggests the effectiveness of plasma exchange for severe radiation pneumonitis.

As a method for measuring the bone mass of the children, we the measurement board for the measurement is improved so that the children may can be correspond ultrasonic wave bone density measuring apparatus CM100 made by FURUNO ELECTRIC Co., and the bone density of 11,418 pupils has been measured from 4 years old to 20 (male infants of 5,939 and female infants of 5,479) . And the evaluation system in each age is completed and we could put the ultrasonic wave measuring device on CM200. Then, it is proposed in order to hoping for the growth of the smooth bone of children in the developing time, and in order to utilize these measuring method and evaluations to the school education.

We evaluated the positive phase period of ImmunoCard Mycoplasma tests. The subjects were 74 penumonia patients (male : 38, female : 36, 17-94 years old) with positive ImmunoCard Mycoplasma tests. ImmunoCard Mycoplasma tests were performed every week for 8 weeks later, then every 4 weeks until negative conversion. The positive phase period was within a week in 30 of 74 patients (40.5%) and within 4 weeks in 52 patients (70.3%). In each generation the positive phase period of the most patients was within a week. The positive phase period of the elderly had no tendency to be longer than that of the young patients. These results indicated that about half of the patients with positive ImmunoCard Mycoplasma tests showed Mycoplasma infection which occurred within the past 1 week.

We evaluated the effectiveness of ImmunoCard Mycoplasma rapid tests in all patients admitted with community-acquired pneumonia (CAP) between January, 2004 and December, 2005. ImmunoCard Mycoplasma rapid tests were performed on the 1st day of admission and we analyzed the frequency of positive cases among CAP cases according to month and age. A total of 82 of 270 (33.7%) and 41 of 257 (16.0%) were positive among CAP cases in 2004 and 2005, respectively. More positive cases were seen between spring and early summer and in cases aged 70 years or more, especially those over 80 years old. These results indicated that further evaluation is required among positive cases in elder group.

It is now clear that oxidative stresses caused by reactive oxygen species, free radicals originating in them, and lipid peroxides can be factors to cause over 90% of lifestyle-related diseases including cancer, heart diseases, cerebrovascular diseases, arteriosclerosis, hypertension, and diabetes mellitus. In the present study, health conditions, nutrition intake, bodily activities, smoking/non-smoking, and sleep hours among other factors were surveyed with youths around twenty years old of age as subjects, and those results and the results of measurement of speed for the generation of 8-OHdG (8-Hydroxy-2'-Deoxyguanosine) as oxidative stress biomarker were compared for consideration. As a result, there were correlations detected as to exercise habits, cholesterol values, and smoking habits. It was also clarified that oxidative stresses decrease by continuing taking constant aerobic exercises or by quitting smoking or reducing the numbers of cigarettes to smoke. Thereby, it was suggested that the measurement of speed for the generation of 8-OHdG can provide an indicator that is useful as an integrated evaluation to improve lifestyle habits that are to be understood to induce lifestyle-related diseases.

We studied the clinical effect of continuous infusion over 24 hours of meropenem (MEPM) on bacterial pneumonia in the elderly (over 65). The subjects were 26 patients (community-acquired pneumonia: moderate, n = 9; severe, n= 4; hospital-acquired pneumonia: group III, n = 13) whose performance status was 3 or 4. MEPM 1.0g/day was infused continuously for 7-14 days, and its clinical efficacy, bacteriological efficacy, and side effects were examined prospectively. It was effective in 23 of the 26 patients (community-acquired pneumonia: moderate, 8/9; severe, 3/4; hospital-acquired pneumonia: group III, 12/13; efficacy rate: 88.5%). Bactericidal effects were obtained in 3 strains of Klebsiella pneumoniae, 2 strains of Streptococcus pneumoniae, 2 strains of methicillin-sensitive Staphlococcus aureus, 1 strain of Streptococcus agalactiae and 1 strain of Proteus mirabilis, but not in 2 strains of methicillin-resistant S. aureus, 1 strain of Pseudomonas aeruginosa and 1 strain of Serratia marcescens. Mild abnormal laboratory findings were observed in 2 patients: elevation of GPT, gamma-GTP, BUN and elevation of ALP. Based on the above, continuous infusion of MEPM on bacterial pneumonia in the elderly obtained excellent clinical effects. Further study is needed to compare the efficacy of continuous versus intermittent administration of MEPM.

We studied the effect of Q fever in acute exacerbation of chronic lower respiratory tract infection. The subjects consisted of 80 cases with acute exacerbation of chronic lower respiratory tract infection treated during the period from March 2002 till October 2004. Q fever was diagnosed using a PanBio Coxiella burnetii ELISA test kit. Two cases (2.5%) were positive for IgM in the acute stage, and were diagnosed as having acute infection by C. burnetii. They were elderly women with bronchiectasis, aged 76 and 82. They had no history of keeping cats or dogs, but the onset of acute exacerbation of chronic lower respiratory tract infection was June and March which is the breeding seasons for cats and dogs. Acute exacerbation of chronic lower respiratory tract infection were considerd to be a mixed infection with Pseudomonas aeruginosa (the 76-year-case) and Haemophilus influenzae (the 82-year-case). It is concluded that C. burnetii can induce exacerbation of chronic lower respiratory tract infection, their cases were considerd to be mixed infection with C. burnetii and other bacteria.

Object: To investigate the epidemiology of M. kansasii infections in Okayama Prefecture and to consider the mode of infection of M. kansasii on the basis of the PFGE results., Materials and Methods: 22 M. kansasii isolates of pulmonary infections from 22 patients treated between 1977 and 1993 in Okayama Prefecture were investigated by pulse-field gel electrophoresis (PFGE) using restriction endonuclease Vsp I. In addition, the tap water from five companies in the Mizushima Industrial Area was cultured to investigate the source of infection of this disease., Results: These M. kansaii isolates were found to be clustered into four or five by PFGE during different. From the tap water, M. kansasii was not detected., Conclusions: From the result of the PFGE, it was considered that the infection sourse of M. kansasii in Okayama Prefecture was living in a common environment or a district.

Cancer vaccine therapy is one of the latest treatment modalities for advanced cancer. In this study, we have newly identified two HER2 peptide epitopes restricted by HLA-A24, which are the most common alleles in Japanese. We have generated mature DCs from PBMCs in the HLA-A24+ healthy donor. Mature DCs were co-incubated with HER2 peptide, and then autologous PBMCs were co-incubated with antigen-loaded DCs. In this way, we have generated HER2 reactive and HLA-A24-restricted CTL lines. The CTL's specificity was evaluated with ELISPOT analysis and cytotoxic assay. In the two CTL lines, the specificity of TISI loaded with HER2/neu peptide used for each CTL induction was recognized, and that specific cytotoxicity was also found against cancer cell lines expressing HLA-A24 and HER2. In conclusion, we have newly identified two HER2 peptide epitopes restricted by HLA-A24 and confirmed that these epitopes will be new targets for cancer vaccine therapy.

This year the education of Medical Technologists has reached the third turning point. The first turning point was the start of the two-year education of health laboratory technicians in 1958 and the second turning point was the start of the three-year education of Medical Technologists in 1971 and, this time, the third turning point is the start of the full-fledged university education. All 20 national education facilities for Medical Technologists and 2 public junior colleges have started the university education from this year. Adding the existing universities, about a half of education facilities for Medical Technologists are universities. From this situation, human resource development with not only knowledge and technique as medical technologists but also with humanly nurtured sentiment is expected in the future. In such situation, I'd like to discuss the progress of education of Medical technologists for 53 years, the current educational situation, and the future education of Medical technologists including the direction of desirable course for the three-year educational facilities.

Chlamydia pneumoniae is a significant cause of both lower and upper acute respiratory illnesses, including community-acquired pneumonia. Furthermore, C. pneumoniae has been reported to frequently cause pneumonia in association with other respiratory pathogens, mainly Streptococcus pneumoniae. In this study, we investigated the clinical presentation of mixed pneumonia with Chlamydia pneumoniae and S. pneumoniae and compared it with S. pneumoniae pneumonia. A total of 13 cases of mixed pneumonia and 58 cases of S. pneumoniae pneumonia identified at Kawasaki Medical School and related hospitals between April 1996 and March 2001 were analyzed. The diagnosis of C. pneumoniae infection was based on isolation and serologic testing of antibodies by the microimmunofluorescence test. The clinical presentation of mixed pneumonia and S. pneumoniae pneumonia was almost identical and no statistical differences were observed between the two groups. This is the same as what was observed before except eleven out of the 13 of the mixed pneumonia patients responded to treatment with only beta-lactam antibiotics. Our results indicated that C. pneumoniae may not be the primary cause of community-acquired pneumonia but it might descript the normal clearance mechanisms, enabling other pathogens to invade.

It was previously reported that monocytes/macrophages play an important role in mediating T-cell dysfunction in tumor-bearing hosts, in which monocytes/macrophages were found to induce the loss of T-cell functions concomitantly with induction of defects in T-cell signaling molecules. These observations encouraged us to investigate monocyte status in cancer-bearing hosts. We characterized peripheral blood monocytes in gastric cancer patients with advanced disease (n = 14), in those with early disease (n = 17) and in healthy individuals (n = 14), based on surface marker, oxygen-burst capacity, and intracellular cytokine status (IL-10 and IL-12). To clarify which mediators induced the characteristic differences of monocytes in cancer-bearing hosts, healthy donor-derived monocytes were co-incubated with the patients' plasma. Intracellular IL-10 and IL-12 status on monocytes in advanced disease was significantly increased in comparison with early disease or healthy individuals, while there were no differences in the surface marker or oxygen-burst capacity of monocytes. The plasma from the patients with advanced disease could induce increased intracellular IL-10 and IL-12 status in healthy monocytes. The phenomenon was significantly inhibited with neutralizing mAbs specific for VEGF.

Cancer vaccine therapy is one of the new treatment modalities for gastric cancer at the advanced stage. In this study, we have identified HER2 peptide epitopes restricted by HLA-A24, which is one of the most common alleles in Japanese. We generated immature DCs from PBMCs in a HLA-A24+, HER2+ gastric cancer patient. Immature DCs were co-incubated with irradiated PC-9 cell line, and then autologous PBMCs were co-incubated with PC-9-derived antigen-loaded DCs. As a result, we were able to generate HER2 reactive, HLA-A24-restricted CTL lines. The CTL's specificity was evaluated with ELISPOT analysis and cytotoxic assay. The CTLs specifically recognized cancer cells expressing HLA-A24 and HER2. We synthesized a set of HLA-A24 binding, HER2-derived peptides to identify HLA-A24 restricted peptide epitopes derived from HER2. In conclusion, we were able to identified HER2 peptide epitopes restricted by HLA-A24, suggesting that these epitopes will be new targets for cancer vaccine therapy.

The medical laboratory technologist education currently offered at four state run junior colleges will be upgraded to higher education as all those junior colleges become universities in 2004. It has already been decided that several private junior colleges and vocational schools are to be upgraded to universities as well. Furthermore, the course will not only be offered in undergraduate universities, but also on a postgraduate level, increasing the number of medical laboratory technologists with a master's degree or a doctorate. This reform is perhaps due to a demand for medical laboratory technologists of higher quality because of such social conditions as a highly-sophisticated information society, advancement in healthcare and medicine, and transition from volume to quality. It is also a measure for securing further capacity by seeking adequate human resources because of the declining population in the 18-year-old bracket, due to the declining birth rate. In such a condition, the direction three-year educational establishments must take is to nurture human resources with qualities that compare favorably with university graduates. As ways of accomplishing this, we could focus on practical technological education at vocational schools with the educational period set at four years, or recruit and train university graduates with rudimental abilities, as they do at specialist postgraduate schools.

The first case of pulmonary Mycobacterium kansasii infection in Okayama Prefecture was discovered in the Mizushima industrial area in 1976. Thereafter pulmonary M. kansasii infection spread to neighboring areas and increase in the number of the patients was reported in 1995. In the present study, new patients with M. kansasii infection between 1994 and 2000 were surveyed by questionnaires sent to 32 main hospitals in Okayama Prefecture. The results showed that 110 patients with pulmonary M. kansasii infection were documented by 20 hospitals. The number of new patients was 10 to 20 annually, and the number of new patients was stable after 1995. The new patients were documented in the center of the Mizushima industrial area and the geographic spread to the new neighboring area was not confirmed.

Lp(a) has recently begun to attract attention as a risk factor of atherosclerotic disease, especially of ischemic heart disease. The Lp(a) concentration in the serum was shown to be important for chronic hemodialysis patients who have high mortality due to cardiovascular disease. Nicotinic acid derivatives, which are recognized for their capacity to lower the serum Lp(a) concentration, are effective against a high Lp(a) concentration in hemodialysis patients. In this study, niceritrol which is a nicotinic acid derivative was tested on hemodialysis patients and healthy controls by investigating the serum nicotinic acid level. Serum nicotinic acid concentration was also measured by the severity of renal dysfunction of patients untreated by niceritrol. The blood nicotinic acid concentration in healthy controls (n = 4) was changed after 2 hrs by the administration of niceritrol from 9.8 +/- 1.4 ng/ml to 192.7 +/- 23.1 ng/ml then slowly decreased. Chronic hemodialysis patients who take niceritrol every day showed the highest nicotinic acid serum concentration (500-1,000 ng/ml) on the day without hemodialysis and the serum level decreased with dialysis for 4 hrs to 25-80%. There was no significant difference in the nicotinic acid level in the serum between healthy controls (n = 10), chronic glomerulonephritis patients (n = 7), chronic renal failure patients (n = 8) and chronic hemodialysis patients (n = 17). Lp(a) concentration in the serum, however, was increased with greater severity of renal dysfunction, The side effect was not observed in any cases administered niceritrol. These data suggest nicotinate derivatives are effective for hemodialysis patients. High nicotinic acid level in the serum after treatment with niceritrol was lowered by dialysis. It is plausible that the nicotinate level in patients without niceritrol treatment did not influence the Lp(a) concentration, because there was no increase in the nicotinate level of the serum even if the patients had renal dysfunction.

Breast milk and blood of Yusho patients were analyzed for polychlorinated biphenyl (PCB) congeners by High separation gas chromatography/Low resolution mass spectrometer. Seventy-one and forty-nine PCB congeners were identified and quantified in the breast milk and blood, respectively. Total PCB concentrations (Whole base) in breast milk of 2 Yusho patients were 69.9 and 15.1 ppb, respectively, being 11.6 and 2.5 times higher than those of 4 control breast milk. Average total PCB concentration of 5.0 ppb in whole blood of 13 Yusho patients was 3.6 times higher than those of control persons. Fourteen PCB congeners, such as 99, 117, 130, 137, 138, 156, 157, 164, 170, 171, 172, 189, 191 and 195, were particularly higher concentration in breast milk and blood of Yusho patients than in those of control persons. Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and coplanar PCBs were also analyzed in the breast milk of Yusho patients and control persons. Large portions, 83 and 74%, of Dioxin toxic equivalency (TEQ) in the 2 Yusho breast milk were consisted of TEQ of 2,3,4,7,8-pentaCDF only, while total TEQ in the breast milk of control persons was consisted of PCDFs 48%. PCDDs 29% and coplanar PCBs 23%.

All PCB congeners were analyzed by high separation gas chromatography/low resolution mass spectrometer, using 209 PCB congeners as standards. They were separated into 169 peaks, including 28 peaks containing 2 PCBs and 8 peaks containing 3 PCBs. The rice oil samples of Fukuoka and Taiwan Poisonings were analyzed for PCB congeners. They showed 115 separated peaks of PCB congeners. Total PCB concentrations were 879 and 769 ppm in 2 samples of Fukuoka rice oil and 57 and 83 ppm in 2 samples of Taiwan rice oil.

1. We examined 156 patients 33 years after CO poisoning occurred at the Miike Mikawa Mine, Fukuoka, Japan. The subjects were classified according to age as follows: between 55 and 59 years (n = 14), 60 and 69 years (n = 62), 70 and 79 years (n = 60), and 80 and 87 years (n = 18). The mean age was 69.2 years old. Concerning the duration of coma that occurred soon after the accident, 64 remained comatose from 0 to 6 hours, 46 from 6 to 12 hours and 46 from 12 to 48 hours. 2. Subjective symptoms were observed in 96.8% of the patients. Among them, forgetfulness was noted in 89.7%, followed by irritability in 66.7%, headache in 59.6%, insomnia in 55.8%, limb pain in 46.8%, dull head feeling in 42.9% and dizziness in 36.5%. 3. Intellectual disturbances were observed in 68.6% of the patients, including impression disturbance in 58.3%, memory disturbance in 51.9%, calculation disturbance in 63.5%, thinking disturbance in 61.5% and disorientation in 14.1%. 4. Apathy and disorder of volition and interest which were found in 72.4% were included in personality change because all symptoms persisted for many years. Personality change was classified as follows: weakness of emotion and will (hypobulia) in 54.4%, infantilism in 35.2%, hyperactive, talkactive and lack of inhibition in 18.5%, lack of self-possession and unstable temper in 9.6%, depression in 15.3%, neurosis in 7.6% and schizophrenic state in 2.5%. Among these symptoms of personality change, weakness of emotion and will and infantilism were conspicuous among the patients who remained in a coma for more than 6 hours soon after the accident but showed no relationship with age. 5. Neurological symptoms that were found in 48.7% of the patients were classified as sensory disturbance in 25.6%, peripheral nerve symptoms in 16.0%, pyramidal symptoms in 14.1%, ataxia and cranial nerve symptoms in 7.1%, paroxysmal symptoms in 6.4% and focal symptoms in 4.5%, extrapyramidal symptoms in 21.8% (Parkinsonism in 4.5%, tremor in 10.9% and muscle rigidity in 16.0%) and vegetative symptoms in 37.2%. 6. At the time of investigation, 5 CO poisoning patients were classified as serious cases (3.2%), 20 as comparatively serious (12.8%) medium-degree cases, 28 as comparatively mild (17.9%) medium-degree cases, 37 as comparatively serious (23.7%) mild cases, 42 as comparatively mild (26.9%) mild cases, 24 (15.4%) as having symptoms which were not problematic, and 24 (15.4%) as having symptoms that markedly worsened due to complication. 7. A total of 138 (88.4%) cases had complications were classified as follows: 78 cases (50.0%) of hypertension, 62 cases (39.7%) of cerebral infarction, 24 cases (15.4%) of cardiac disturbance, 21 cases (13.5%) of diabetes mellitus, 14 cases (9.0%) of hepatic disturbance and six cases of silicosis (3.8%). 8. Cranial MRI was carried out for 129 cases (82.7%). Of the abnormal findings identified, cerebral atrophy accounted for 72.0% (93 cases), including moderate and severe cases in 47.2% (61 cases), pallidum lesion for 37.9% (49 cases), lacunar infarction (including cerebral infarction) for 52.7% (68 cases), and hippocampal atrophy for 18.6% (24 cases). Many cases of cerebral atrophy and hippocampal atrophy were observed in patients who remained in the initial coma for more than 12 hours and were 80 years of age or old. The cases of pallidum lesion were observed in patients who remained in the initial coma for more than 6 hours, and no relationship with age was found. The other findings, cerebral atrophy and lacunar infarction showed a slight relationship with age. 9. Among the moderate and serious cases of intellectual disturbance, cerebral atrophy constituted to 62.5%, lacunar infarction 68.7% and pallidum lesion 50.0%. Among the moderate and serious cases of personality change, cerebral atrophy constituted 78.5%, lacunar infarction 35.0% and pallidum lesion 50.0%. Moreover, among extrapyramidal symptoms, pallidum lesion constituted 58.6%, cerebral atrophy 55.1% and lacun

We report a case of squamous cell lung cancer with nephrotic syndrome. A 69-year-old man was admitted because of proteinuria and microhematuria. A plain chest X-ray film on admission showed a large mass in the left-lower lung field. The patient was given a diagnosis of minimal-change-nephrotic syndrome and squamous cell lung cancer. We first treated the nephrotic syndrome with glucocorticoid therapy, and then treated the lung cancer with chemo-radiotherapy. This reduced the lung cancer, alleviated the proteinuria, and completely resolved the nephrotic syndrome. Nephrotic syndrome is generally associated with malignant lymphoma and other nonepithelial neoplasms. As the underlying disease, epithelial neoplasms are less common, but lung cancer is one of the most widely reported. Histologically, most cases of cancer-associated nephrotic syndrome exhibit membranous nephropathy; Minimal-change nephrotic syndrome is rare. Deposits of immunocomplex on glomerular basement membrane are considered to play a pathogenic role in membranous nephropathy. However, the pathogenesis of minimal-change nephrotic syndrome is different.

Physical activity is known to increase glucose tolerance and insulin sensitivity. To examine the influence of physical inactivity on insulin sensitivity in aged people, insulin sensitivity and secretion was measured by using a two-step euglycemic glucose clamp, a glucagon tolerance test (GTT), an oral glucose tolerance test (OGGT) and urinary CPR excretion in 11 aged patients immobilized in bed for more than 12 weeks. The results were compared with those of nine healthy mobile aged controls. The muscle volume of the immobilized patients decreased by 20-25% compared with that of the controls, and insulin sensitivity decreased 50% in each step. These results mean that the immobilized patients had decreased insulin sensitivity and responsiveness, even when there was muscle atrophy. The glucose and insulin responses in both the GTT and OGTT showed that there was a slight decrease in the initial response of insulin in the immobilized patients and was in the controls compared with adolescent controls. There was no difference in the initial response of insulin between the immobilized patients and the aged controls. The ratio of impaired glucose tolerance in the OGTT was 4/11 of the immobilized patients and 3/9 of the controls. Total insulin secretion was increased and insulin sensitivity and responsiveness was decreased in the immobilized patients. This suggests that the decreased insulin sensitivity was compensated for increased by insulin secretion in the immobilized patients.

A 60-year-old man was admitted to the Kyushu University Hospital because of poor glycemic control of diabetes mellitus. Although he had been treated with glicrazide and nifedipine for his diabetes and hypertension, the controls of the diseases were unsatisfactory. Plasma triglyceride level was 186 mg/dl. Furthermore, extreme insulin resistance was found by measuring glucose infusion rate with an euglycemic hyperinsulinemic clamp method. These findings were compatible to those seen in syndrome X. After admission, diet therapy of 1,800 Cal was started and his metabolic disorders such as hyperglycemia, hyperlipidemia, and hypertension were all improved. Moreover, euglycemic hyperinsulinemic clamp study also revealed a decreased insulin resistance after diet therapy. Our experience from the case suggested that insulin resistance may closely related with the metabolic disorders of the disease "syndrome X".

A 48-year-old female who had general fatigue was admitted to our hospital. She had swelling of the axillary, inguinal, and paraaortic lymph nodes and mediastinal lesions. Laboratory examinations showed anemia, polyclonal hyperimmunoglobulinemia with IgG 5570 mg/dl, renal dysfunction and interstitial changes of the lungs. Microscopic findings of hematoxylin-eosin staining in biopsy specimens of the left inguinal and axillary lymph nodes revealed increased levels of infiltration of mature plasma cells without evidence of malignancy. Immunoperoxidase staining showed intracytoplasmic polyclonal immunoglobulin. These findings were identical to those of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL) described by Mori et al. (1980). The specimens also showed evidence of chronic nephritis with infiltration of lymph cells and a slight invasion of plasma cells. Accordingly this case was diagnosed as IPL with renal involvement, which is associated with chronic nephritis. Recently, five cases of IPL with renal dysfunction have been reported. In particular, two cases of IPL with renal dysfunction, which included our case, revealed an increased level of IL6. These findings suggest that the occurrence of renal involvement with IPL may be related to changes in IL6, which is an important factor in the pathogenesis of IPL.