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Epstein-Barr virus (EBV)-related lymphoproliferative disorder (LPD) is a serious complication of haematopoietic stem cell transplantation (HSCT). To clarify the frequency, natural course and risk factors for LPD, we prospectively monitored 38 allogeneic (allo)-HSCT patients, focusing on the use of anti-thymocyte globulin (ATG). We used a recently developed real-time polymerase chain reaction assay to monitor EBV genome load. The subjects consisted of 19 patients given ATG for conditioning and 19 patients not given ATG. Of the 19 patients given ATG, 47.4% (nine patients) had a significant increase in EBV genome load (10(2.5) copies/microg DNA). Of these nine patients, two developed LPD. Therefore, 10.5% of the patients receiving allo-HSCT with ATG developed LPD. In contrast, none of the 19 patients without ATG had a significantly increased EBV load. The increases in viral load were observed in the second or third month after HSCT. We found that the peak viral loads of LPD patients were10(4.0 ) copies/microg DNA. On the other hand, the viral loads of most patients with no symptoms were10(2.5) copies/microg DNA. In conclusion, routine monitoring of EBV load during the second and third months after transplantation may benefit patients undergoing HSCT with ATG. We propose that an EBV load10(2.5) copies/microg DNA is the reactivation of EBV, and that an EBV load10(4.0) copies/microg DNA is indicative of developing LPD.

Inhaled corticosteroid therapy against bronchial asthma has developed rapidly and remarkably during last 10 years. The significance of this therapy has been established in a lot of international guidelines for asthma management. Early intervention, which developed from the concept of step-down therapy, is new therapeutic approach to prevent the remodeling of airway walls deemed as the major cause of irreversible airflow limitation which makes patient chronic and refractory asthmatics. It is comprehensive therapeutic approach which include not only early diagnosis, early intensive corticosteroid therapy, but also environment intervention and enough patient education. In addition to this new therapeutic strategy, we will describe about add-on effect of long-acting beta-2 agonists, theophylline, and leukotriene receptor antagonist.

From October 1999 to September 2000, we collected the specimen from 430 patients with lower respiratory tract infections in 17 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 515 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 506 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 101, Haemophilus influenzae 104, Pseudomonas aeruginosa (non-mucoid) 58, P. aeruginosa (mucoid) 11, Moraxella subgenus Branhamella catarrhalis 41, Klebsiella pneumoniae 18, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or above of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 57.7%. Vancomycin and arbekacin showed the most potent activities against MRSA without detection of ABK-resistant strain (MIC: 64 micrograms/ml) and decrease of VCM-sensitive strains those were found in 1998. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) decreased to 34.7% from 46.0% in 1998. The frequency of PRSP was 3.0%, being the least number after 1991. Carbapenems showed strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 101 strains with MIC of 0.063 microgram/ml. Generally, all drugs showed strong activities against H. influenzae with MIC80s of 4 micrograms/ml or below. MICs of ofloxacin ranged between 0.063 microgram/ml and 4 micrograms/ml in 1998, however, those were 0.125 microgram/ml or below in all H. influenzae in 1999 showing the strongest activity. Tobramycin and ciprofloxacin showed strong activities against P. aeruginosa (both mucoid and non-mucoid) with MIC80s of 1 microgram/ml. Number of isolated P. aeruginosa (mucoid) was little as 11, however, the susceptibilities to all drugs were better than P. aeruginosa (non-mucoid). K. pneumoniae showed good susceptibilities to all drugs except for ampicillin with decreasing of low-sensitive strains compared to those detected in 1998. Also, all drugs generally showed strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or below. The drug which showed the strongest activity was imipenem inhibiting all 41 strains with MIC of 0.063 microgram/ml. On the patients' characteristics, the number of patients aged 80 years or older who had been increased was decreased in 1999 in the distribution by age. The percentage of the elderly patients aged 70 years or older was 47.0%, which occupied almost a half number of the total patients as in the last year. As for the incidence by disease, bacterial pneumonia and chronic bronchitis were the highest. They were noted in 37.9% and 30.5% of the patients, respectively. In 1999, bronchial asthma was frequently observed as compared in recent years. It was noted in about 10% of the patients which is the same % as in bronchiectasis. We examined the number of strains from these patients with infections before and after administration of antibiotics. In patients with bacterial pneumonia, the number of isolated strains was almost the same between those before and after administration. However, in patients with chronic bronchitis, the number of strains remarkably decreased to less than the half of the total after administration of antibiotics in the last year, but it decreased to 2/3 of the total in 1999. On the administration of antibiotics and isolated bacteria by the day of administration, the bacteria which were isolated more before administration were H. influenzae in 28.4%, S. pneumoniae in 25.7%, M. (B.) catarrhalis in 12.0% and S. aureus in 10.6%. The frequency of S. aureus after administration over 15 days was almost the same as that before administration, but the frequency of P. aeruginosa (both mucoid and non-mucoid) was 36.8% which was higher than that before administration. The frequency of isolated S. pneumoniae was decreased after administration and none of them was isolated after completion of administration. However, that of H. influenzae was decreased to 7.1% after administration within 3 days, and many H. influenzae were isolated after completion of administration as 21.4%.

We report a favourable outcome in 15 patients with severe aplastic anaemia (SAA) who were20 years of age and who underwent bone marrow transplantation (BMT) from a human leucocyte antigen (HLA)-matched unrelated donor. All patients were non-responders to intensive immunosuppressive therapy (IST) and were multiply transfused. The conditioning regimen consisted of cyclophosphamide (60 mg/kg/d, on d -4 and -3), anti-thymocyte globulin (2.5 mg/kg/d, on d -5 to -2) and total body irradiation (2.5 Gy x 2/d, on d -2 and -1). Patients received cyclosporine and methotrexate for prophylaxis of graft-versus-host disease (GVHD), except for the last four who received tacrolimus instead of cyclosporine. Donor/recipient pairs were identical for HLA class I and II antigens by serological typing, but four pairs were found to have a mismatch at the HLA-A, -B or -DRB1 locus by high-resolution typing. All patients achieved rapid engraftment and are alive at 2-86 months after transplantation (median follow-up, 51 months). Moderate to severe acute GVHD occurred in 5 out of 15 patients (33%); only one patient developed extensive chronic GVHD. Considering our encouraging results, unrelated donor transplantation for SAA is recommended as a salvage therapy in non-responders to IST.

Since ginsenoside-Rg(3), one of the panaxadiol saponins isolated from the ginseng root, significantly inhibited the secretion of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh), the properties of ginsenoside-Rg(3) inhibition were investigated. Although ginsenoside-Rg(3) inhibited the secretion evoked by ACh in a concentration-dependent manner, it affected the secretion stimulated by high K(+) or veratridine, an activator of the voltage-sensitive Ca(2+) or Na(+) channels, only slightly. The ACh-induced Na(+) and Ca(2+) influxes into the cells were also reduced by ginsenoside-Rg(3). The inhibitory effect of this saponin on the secretion of catecholamines was not altered by increasing the external concentration of ACh or Ca(2+). The ACh-evoked secretion of catecholamines was completely restored in cells that were preincubated with 10 microM ginsenoside-Rg(3) and then incubated without the saponin, whereas secretion was not completely restored in cells that were preincubated with 30 microM of this compound. Above 30 microM ginsenoside-Rg(3) increased the fluorescence anisotropy of diphenylhexatriene in the cells. Furthermore, the inhibitory effect of ginsenoside-Rg(3) at 30 microM on the ACh-evoked secretion of catecholamines was dependent upon the preincubation time, but this was not the case at 10 microM. These results strongly suggest that ginsenoside-Rg(3) blocks the nicotinic ACh receptor-operated cation channels, inhibits Na(+) influx through the channels, and consequently reduces both Ca(2+) influx and catecholamine secretion in bovine adrenal chromaffin cells. In addition to this action, the ginsenoside at higher concentrations modulates the fluidity of the plasma membrane, which probably contributes to the observed reduction in the secretion of catecholamines.

This paper presents a new dual color FISH technique that will allow the use of cell specimens isolated from formaldehyde-fixed and paraffin-embedded (F-P) tissues. The new FISH method was used to examine numerical aberration in chromosome 17 and c-erbB2 gene amplification in 26 F-P epithelial ovarian cancer tissues. Numerical aberration of chromosome 17 appears frequently in clear cell adenocarcinoma. The frequency of amplification of the c-erbB2 gene in stage III and IV cases was significantly higher than in stage I cases. The FISH technique as established here may serve as a molecular tool for examination of clinico-pathological significance in F-P tissues.

It is generally considered that tuberculosis (TB) is a disease which upregulates Th1 cell function. There is a hypothesis that infection of Mycobacterium tuberculosis may prevent allergic disorders such as bronchial asthma. However, our clinical experience of patients with TB somewhat conflicts this hypothesis. Hence, we investigated Th1/Th2 balance in the peripheral blood of patients with active TB by measuring serum levels of IgE antibody and by intracellular cytokine assay. We found that serum levels of IgE in the patients with active TB were significantly higher than in those with lung cancer or with COPD. In the TB patients, titers of IgE tended to correlate with disease severity. Intracellular cytokine assay demonstrated that IFN-gamma-positive cells were significantly decreased in the patients with active TB compared to normal controls. The ratio of IFN-gamma-positive (Th1-like)/IL-4-positive (Th2-like) cells was remarkably reduced in the TB patients (p0.0001). This ratio showed a significant negative correlation with erythrocyte sedimentation rate and with C-reactive protein. Therapy against TB for 2-3 months did not result in significant changes of the Th1/Th2 ratio. These findings suggest that infection of M. tuberculosis does not systematically upregulate Th1 cells in some patients, and is unlikely to prevent allergic disorders like asthma.

In order to determine the clinical significance of numerical aberrations on chromosome 17 in uterine cervical and endometrial neoplasias, we investigated 140 cell specimens obtained from the uterine cervix and endometrium using the fluorescence in situ hybridization (FISH) method. These specimens consisted of ten normal cervical epithelium (NCE), 16 cervical intraepithelial neoplasias (CIN 1), 15 CIN 2, 35 CIN 3, 11 early invasive squamous cell carcinoma of the uterine cervix (early invasive SCC), 11 invasive SCC, 13 normal endometrium (NE), 17 endometrial hyperplasias (EH), and 12 endometrial ademocarcinomas (EA). After Papanicolaou staining on these specimens was decolorized, FISH was performed using chromosome 17 specific repetitive DNA probes. Signals of centromere of chromosome 17 in marked atypical cells were counted using a fluorescence microscope. There was a significant difference in the rate of cells with one signal on chromosome 17 between CIN 1 (7.1+/-0.7%) or 2 (7.0+/-0.5%) and CIN 3 (12.6+/-0.9%) (p0.01), and also between CIN 3 and early invasive SCC (19.6+/-1.0%) (p0.01). The rate of cells with three signals was significantly increased when the uterine cervical lesions were progressive to CIN 3 (p0.01). Cells with five or more signals occurred only in early invasive SCC and invasive SCC. There was a significant difference in the rate of cells with three signals between EH (4.8+/-0.6%) and EA (11.4+/-2.1%) (p0.05). Cells with five or more signals occurred only in EA. Examination of the numerical aberrations on chromosome 17 in uterine cervical and endometrial neoplasias has been suggested to be useful as an additional method for the differential diagnosis of these lesions.

A 73-year-old man was admitted to our hospital for evaluation of abnormal lung shadows in the left lung. Chest computed tomography revealed a cavitary lesion with irregular edges in the right S10 and a nodular lesion with well-defined margins in the left S6. Histological examination of a specimen obtained by transbronchial lung biopsy revealed squamous cell carcinoma in the right S10 but no significant findings in the left S6. Thirdly, 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) demonstrated that the nodular shadow in the left S6 was a low-uptake structure and that the cavitary lesion in the right S10 was a high-uptake lesion. We therefore considered that the nodular shadow in the left S6 was not one of neoplastic disease. Partial lung resection of the left S6 was carried out by videoassisted thoracoscopic surgery. The pathological diagnosis of the left S6 was epithelial granuloma with caseation. A culture of the same resected specimen was positive for Mycobacterium avium. The eventual clinical staging for the squamous cell carcinoma in the right S10 was cT2N0M0 (IB). Radical surgical treatment and right lower lobectomy were performed for the S10 lesion. We considered that 18F-FDG-PET was an effective noninvasive procedure for diagnosis of solitary or multiple solitary nodular shadows in the lung.

Essential thrombocythemia (ET) is one of the quite rare myeloproliferative disorders in children. The natural course and outcome of this disease have been reported to vary. We report three children (two boys and one girl, mean age at diagnosis 12 yr) with ET who showed different clinical courses. The girl was asymptomatic, but the boys had ankle pain and priapism, respectively. The platelet count ranged between 2300 and 2900 x 10(9)/L, and the diagnoses were made according to the criteria of the Polycythemia Vera Study Group. The serum thrombopoietin level reached 0.33 and 0.47 fmol/ml in two patients. All three children were administered aspirin or dipyridamole orally. Normalization of the platelet count was observed in two patients, and stable disease persisted in one. The 12 pediatric patients with ET reported previously in Japan demonstrated a low incidence of serious thrombohemorrhagic complications and a favorable outcome, none developing acute leukemia. Careful continuous observation and conservative treatment may be preferable in pediatric patients who do not have cardiovascular symptoms, avoiding the use of potential leukemogens such as alkylating agents and hydroxyurea.

We investigated whether a causal relationship exists between human herpesvirus 6 (HHV-6) and skin rash resembling acute graft-versus-host disease (GVHD) following bone marrow transplantation (BMT). Isolation of HHV-6 was used to monitor active HHV-6 infection in this study. We analyzed 25 episodes of skin rash in 22 recipients. All recipients were seropositive for HHV-6 before BMT. The onset of skin rash started prior to 30 days post transplantation (group A) in 15 of 25 cases, but after that (group B) in the remaining 10 cases. Twenty-five skin tissue samples were obtained from 22 recipients. The HHV-6 genome was detected in four of 15 skin samples from group A, but not detected in those from group B. HHV-6 was isolated from 11 of 22 recipients around 2 to 3 weeks after BMT (range 14 to 28 days after BMT). HHV-6 was isolated at a time between 10 days before and after the onset of skin rash (skin rash-related viremia) in nine cases in group A. Meanwhile, no skin rash-related viremia was observed in group B. Of the four recipients with positive detection of HHV-6 genome in their skin tissue (group A), two had HHV-6 viremia at the same time. The association between the timing of HHV-6 infection and the onset of skin rash was analyzed statistically. HHV-6 viremia (skin rash-related viremia) was found in nine of 15 (60%) cases in group A, compared with none of 10 (0%) cases in group B. This difference was statistically significant (P = 0.008). Moreover, HHV-6 infection (skin rash-related viremia and/or positive detection of HHV-6 DNA in skin tissue) was demonstrated in 11 of 15 (73.3%) cases in group A, compared with none of 10 (0%) cases in group B (P = 0.001). Thus, this study suggests that HHV-6 may be involved in the development of skin rash in the first month after allogeneic BMT.

The molecular alignment on solid substrates is important both to fundamental issues in physics and chemistry and to practical applications such as optoelectronic molecular devices. It is well-known that the orderings of adsorbed molecules in the anchoring region near the substrate are strongly affected by the substrate surface structure and the balance of molecule-molecule and molecule-substrate interactions. This is especially evident in the case of liquid crystal molecules, for example, where such an alignment technique with boundary effects at the substrate surface has been widely used to produce director configurations in the monodomain cells such as flat-panel displays and optical shutters. However, the actual mechanism of their orientation at the interface has long been unclear, because there have been technical difficulties in the analysis of the anchoring structures at a molecular level. Since its invention, the scanning probe microscope (SPM) has been successfully applied to direct visualization of the interfacial structure with molecular resolution, and used to study positional and orientational order in organic molecules on solid substrates. [1] In fact, high-resolution scanning tunneling microscope (STM) images now allow us to make a real-space analysis of the molecular alignment at the interface and to discuss details of the growth mechanisms of molecular films on an individual molecular scale. This section will briefly review local area visualizations that have been performed with the STM and allied microscopies on organic ultra-thin films, rendering features from the nanometer to the submicron scale.

We investigated a band gap shrinkage in both lattice‐matched and compressive strained GaInAs/GaInAsP/InP multi‐quantum well lasers. The band gap shrinkage is obtained from the broadening of the low energy side in the spectrum by considering effects of an intraband scattering and a fundamental band edge. It amounts to 20–25 meV at sheet carrier densities of above 1012 cm−2, and shows n1/1.3 dependence at low carrier densities and n1/3 dependence at higher densities. These dependencies agree well with theoretical predictions in the quantum well.

Enantiomeric ratio of hyoscyamine from Scopolia extract was determined by chiral HPLC-CD analysis. It was found that circular dichroism (CD) detection allowed the analysis of the sample without any special pretreatment whereas UV detection required an ammonia-ether extraction. To obtain a shorter analysis time for the determination, reversed-phase HPLC-CD analysis was applied by using a g-factor calibration curve (EE% vs. CD/UV). The analysis time was shortened from 35 to 18 min. EE% values obtained were consistent with those by chiral HPLC analysis.

A 54-year-old man with acute respiratory failure underwent emergency admission to our hospital. Acute pulmonary edema combined with severe pneumonia was strongly suspected, and treatment with diuretics, antibiotics, and corticosteroids was effective. The diagnosis, primary macroglobulinemia, was made from the following findings: a high level of the lgM 1 type monoclonal protein, and an elevated serum viscosity with characteristic "linked sausage effects" seen in the retinal veins. Lymphoplasmacytoid cells, plasma cells, and small lymphocytes were seen in the bone marrow and lymphoplasmacytoid cells were also seen in the smear of the patient's peripheral blood. The types of malignant cells found in his bone marrow were also seen in both infiltrative lesions in the lung parenchyma and the pleural effusion. We concluded that this was a case of primary macroglobulinemia with acute pulmonary edema, which was caused partly by the hyperviscosity syndrome. The antitumor effect of the corticosteroid might have some effect on the recovery from acute respiratory failure and primary macroglobulinemia. He was transferred to the Department of Hematology to receive suitable chemotherapy.

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 18 institutions around the entire Japan, 532 strains of presumably etiological bacteria were isolated mainly from the sputa of 438 patients with lower respiratory tract infections during the period from October in 1998 to September in 1999. MICs of various antibacterial agents and antibiotics were determined against 85 strains of Staphylococcus aureus, 100 strains of Streptococcus pneumoniae, 96 strains of Haemophilus influenzae, 75 strains of Pseudomonas aeruginosa (non-mucoid strains), 6 strains of Pseudomonas aeruginosa (mucoid strains), 38 strains of Moraxella subgenus Branhamella catarrhalis, 26 strains of Klebsiella pneumoniae etc., and the susceptibilities of 517 strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 60.0%. Vancomycin (VCM) and arbekacin (ABK) showed the most potent activities against MRSA. But one of MRSA showed resistance to ABK with the MIC of 64 micrograms/ml. The sensitive strains of MRSA to VCM have decreased. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP) + PC-resistant S. pneumoniae (PRSP) have increased in 46.0% for 1998 comparatively from 30.9% of 1997's. But PRSP decreased, and PISP increased into 39.0% of 1998 years from 19.8% of 1997's. Panipenem (PAPM), imipenem (IPM) and faropenem (FRPM) showed the most potent activities against S. pneumoniae with MIC80s of 0.125 microgram/ml or below. Against H. influenzae and M. (B.) catarrhalis, almost all the drugs showed good activities. The sensitive strains of them against ceftazidime (CAZ) decreased in 1997, but those have increased in 1998. Inversely, the susceptibility of them against cefotiam (CTM) had been higher in 1997, but those have been lower in 1998. Tobramycin (TOB) showed the most potent activity against P. aeruginosa (both mucoid and nonmucoid strains). All drugs except ampicillin (ABPC) were active against K. pneumoniae. A quite few of K. pneumoniae showed low susceptibilities. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 48.6% of all the patients showing a slight increase in every year. About the proportion of diagnosed diseases as follows: Bacterial pneumonia was the most frequent with 40.2%. The ratio of it has increased slightly, and the increased rate was 10% in patients with ages over 70 years compared with the results in 1997. Chronic bronchitis have decreased slightly with 27.6% in 1998. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these were almost same number in bacterial pneumonia. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 26.7%, H. influenzae 23.8%, S. aureus 13.3% and M. (B.) catarrhalis 10.8%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa (both mucoid and non-mucoid) was not affected. The frequencies of P. aeruginosa was 45.5% after administration over 15 days. The frequencies of S. pneumoniae decreased upon administration of antibiotics, these were only 4.5% over 15 days. The frequencies of H. (

A 68-year-old Japanese woman was admitted to our hospital because of hoarseness, dysphagia and a mass on the right side of her neck. Chest radiographs showed multiple nodular shadows in both lung fields. Detailed investigations resulted in a diagnosis of multiple lung metastasis of anaplastic thyroid carcinoma transformed from papillary adenocarcinoma. Both serum CA 19-9 and GM-CSF levels were elevated, to 70.5 U/ml (normal range: 0-37 U/ml) and 343.4 pg/ml (normal range: 0-8 pg/ml), respectively. Immunostaining disclosed that the primary and metastatic tumors were positive for CA 19-9, but not for GM-CSF antigens. Serum levels of these two parameters slowly decreased after chemo-radiotherapy, suggesting that the tumor may have produced GM-CSF as well as CA 19-9. Recent studies have indicated that the prognosis is poor for non-small cell lung cancers that produce G-CSF or CA 19-9. To our knowledge, this is the first case report of anaplastic thyroid carcinoma characterized by high serum levels of both CA 19-9 and GM-CSF, with metastasis to the lung and other organs.

To analyze specific mucosal changes in asthmatic patients receiving long-term, high-dose beclomethazone dipropionate (BDP) inhalation therapy, we performed bronchial mucosal biopsies and immunohistochemical analysis of patients who had been treated with or without BDP-inhalation. Our study enrolled 6 chronic severe asthmatics who were treated with 1,800 micrograms/day or more of BDP with regular use for more than 3 years (HD-BDP group), 6 mild asthmatics who were not treated with BDP (non-BDP group), and 6 control subjects. Specimens of bronchial mucosa were stained with anti-EG 2 (eosinophils), anti-UCHLA-1 (T lymphocytes) and anti-tryptase (mast cells). Although limited eosinophil infiltration was observed in the HD-BDP and control groups, a significant increase was noted in the non-BDP group. The infiltration of both T lymphocytes and mast cells exhibited a statistically significant increase in the non-BDP group compared to the HD-BDP and control groups. In chronic severe asthmatics, airway mucosal cell infiltration was reduced by high-dose and long-term inhaled BDP therapy, and BDP also relieved their asthmatic symptoms. However, in mild asthmatics, bronchial mucosal cell infiltration remained high. For such patients, we concluded that initiating BDP therapy from an early stage may bring clinical improvement and help prevent cell infiltration.

We present a case of aminophylline hypersensitivity reaction due to ethylenediamine. A thirty-year-old Japanese female admitted to our hospital to evaluate generalized urticarial reaction immediately after intravenous administration of aminophylline. Skin intradermal testing was positive with ethylenediamine. A positive intravenous test was found with aminophylline and negative with diprophylline which does not contain ethylenediamine. There are some reports of aminophylline hypersensitivity reaction and the most cases were delayed type reaction in English literatures. However, most of Japanese cases were immediate type. Acetylation is a main metabolic pathway of ethylenediamine. Most of Japanese have a rapid or intermediate acetylators on the other hand. Caucasian have a 50% likelihood of being slow acetylators. This difference suggest the different incidences of immediate and delayed reaction of aminophylline hypersensitivity reaction in Japanese and Caucasian respectively.

In order to realize efficient coupling between a flux-flow type Josephson oscillator (FFO) and a stripline impedance transformer, the authors have made a theoretical study of the inductive coupling between FFO and a stripline. It is shown that by choosing the output impedance of the FFO Zo smaller than the characteristic impedance of the coupling section Z1, the frequency dependence of the output power at the end of the coupling section can be extremely flat over a large frequency band. A model simulation employing a NbN/Pbin Josephson junction and a Nb/NbN stripline demonstrates that in the case of optimum design Z0=0.6 Z1, the bandwidth of the coupling section, which is defined by the frequency range where the deviation is within +or-5%, is shown to be as large as 80% of the centre frequency.

Transbronchial lung biopsies and cytologic studies under ultrasonographic guidance from the body surface were conducted in 39 patients whose lesions were adjacent to the thoracic wall. In 26 patients, biopsy, curettage, or brushing forceps were visualized in the mass or infiltrative lesion by thoracic echogram. Positive findings were obtained in 23 patients, for a conclusive diagnostic rate of 88.5%. Of the 13 patients in whom forceps could not be visualized by echogram, 10 had positive findings, for a diagnostic rate of 76.9%. For visualization by thoracic echogram, abnormal lung lesions must be in direct contact with the thoracic wall. Occasionally, diagnostic procedures may be impeded by anatomical structures such as shoulder joints or scapula. Despite these disadvantages, the ultrasonography-guided bronchofiberscope is quite useful because it facilitates real-time confirmation of the positioning of the forceps relative to the lesions. It is also useful in cases when the peripheral lesions are too small or vague to be demonstrated by fluoroscopy alone, because the echo probe can be the target of the forceps instead of the missing shadows. The diagnostic rate should be higher when the forceps are visualized in the lesions ultrasonographically.

A novel missense mutation, G663A, in exon 5 of the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) was identified in a Japanese male with pyridoxine-responsive sideroblastic anemia. Activity of the mutant delta-aminolevulinate synthase protein expressed in vitro was 15.1% compared with the normal control, but was increased up to 34.5% by the addition of pyridoxal 5'-phosphate, consistent with the clinical response of the patient to pyridoxine treatment. The same mutation was also detected in genomic DNa from the oral mucosal membrane of the patiet; however, it was not detected in other family member. These findings suggest that this G663A mutation is responsible for sideroblastic anemia in the proband, and may be an index mutation in this pedigree.

An 8-month-old boy was admitted because of paleness. Laboratory studies disclosed microcytic and hypochromic anemia: red blood cell count 156 x 10(4)/microliter, hemoglobin 3.5 g/dl, mean cell volume 66 fl, and reticulocytes 0.5/1000. Serum iron was 433 micrograms/dl and exocrine pancreatic dysfunction was not observed. Examination of bone marrow revealed prominent erythroid hyperplasia; 18% of the erythroblasts were distinct ringed sideroblasts. Electron microscopic studies found intramitochondrial iron deposits in the erythroblasts. The patient was given a diagnosis of sideroblastic anemia and responded to oral pyridoxine (50 mg/day) with an immediate increase of reticulocytes to 97/1000, resulting in an improved hemoglobin concentration. He has maintained remission for more than 1 year following discontinuation of pyridoxine, which was administered for 2 months. Congenital sideroblastic anemia is relatively rare and mostly occurs in males, suggesting an X-linked recessive mode of inheritance. Recently, X-linked sideroblastic anemia has been shown to be caused by missense mutations in the delta-aminolevulinic acid synthase (ALAS) gene. A point mutation in exon 5 of the ALAS gene was found in this patient. Iron-deficiency anemia is the most common hematologic disease of infancy and childhood, resulting from lack of sufficient iron for synthesis of hemoglobin. It is therefore mandatory to differentiate sideroblastic anemia from iron-deficiency anemia and other common anemias.

cDNA of yellowtail ascites virus (YAV) segment A encoding a polyprotein of VP2, NS, and VP3 has been cloned. Comparison of the nucleotide and the deduced amino acid sequences showed very high homology between YAV and other aquatic birnaviruses. The two small open reading frames (VP5) besides the 5′ terminus of the VP2 gene were found on segment A of YAV. Proteins encoded by cDNAs from segment A and the serotype-specific epitope region on VP2 were expressed using a baculovirus vector. Western blot analysis confirmed that a polyprotein was expressed and processed into VP2 and VP3 in insect cells infected with the recombinant baculovirus containing the complete polyprotein coding region. In the case of expression in silkworm larvae, only VP3 was detected in hemocytes and fat body of silkworm larvae infected with the recombinant virus. The recombinant fusion protein consisting of VP2 epitope region and polyhedrin was expressed in insect cells and cross-reacted with a mouse monoclonal antibody against VP2 which had a neutralizing activity to YAV.

In order to assess the clinical features and clinical courses of endobronchial tuberculosis, which included trachea to segmental bronchus, we studied 34 cases of patients who were admitted to TB ward of International Medical Center of Japan from 1994 to 1997. We noticed a higher incidence in females and in the main bronchus. Cough was the most common complaint seen in 97% of cases. The duration of symptoms before the initiation of antituberculous chemotherapy was long (on the average 6 months), and they were often treated as bronchial asthma or bronchitis. Bronchoscopic examination is necessary for diagnosis. The scars sometimes gave rise to severe stenosis, especially when the lesion developed to an advanced stage or circumscribed the lumen before treatment. We tried INH inhalation with systemic chemotherapy. Although rapid improvement was suggested by this method, yet no significant difference was seen in the results for the efficacious prevention of stenosis. Five cases required surgical intervension (bronchoplasty and lobectomy) in order to avoid atelectasis or secondary infection. Early diagnosis and appropriate treatment are most important, and bronchoscopic examination is essential in early diagnosis.

Achievements of KEKB control system during the commissioning of KEKB accelerators are reported. The KEKB control system is the first major application of EPICS toolkit in JAPAN. We added some software components on the top of EPICS toolkit. One of these is the system to automate generation of the EPICS database configuration files using ORACLE database management system. Although it costs us a lot of effort to develop, this kind of configuration management system is essential for a large accelerator like KEKB. Another component is an implementation of EPICS CA (Channel Access) interface in the script languages. SAD, a modeling program with a scripting language capability, Python, an object oriented scripting language are currently supported in the KEKB control system. These scripting languages are used to develop high level applications, such as an orbit correction program with graphical user interface using Tk library. Combination of these scripting languages and EPICS CA provides flexibility in the control system. KEKB control system also includes some new hardware components, including Arcnet based magnet power supply controllers and VME single board computers based on Motorola's PowerPC750 CPU. The performance of these components will also be reported. The problems and (possible) solutions found during the KEKB commissioning are also discussed.

Following the development of an isotropic personnel fast-neutron dosimeter having an approximately flat dose-equivalent response to fast neutrons (from 0.1 to 19 MeV) in free air, which was reported elsewhere, we developed a thermal-neutron dosimeter having an approximately similar dose-equivalent response as that of fast neutrons under the same processing conditions. We now combine the above dosimeters into a single one and study its response on a tissue phantom. Our results show that the dose-equivalent response of the dosimeter in question will no longer be energy- and direction-independent when irradiated with mixed-energy and multidirectional neutrons on a tissue phantom.

In spite of recent advances in diagnosis and chemotherapy of tuberculosis, prognosis of tuberculosis of the central nervous system (CNS) is still poor. We evaluated clinical characteristics of 14 patients with the CNS tuberculosis (10 male and 4 female, 21 to 71 years of age) who were hospitalized at IMCJ from 1988 to 1997. Twelve patients had tuberculous meningitis (2 of them had also intracranial tuberculoma), 1 had intracranial tuberculoma and 1 had spinal cord tuberculosis. For the acid-fast bacilli, the smears of cerebrospinal fluids (CSF) were all negative but the cultures for M. tuberculosis were positive in 5. Using PCR method, M. tuberculosis was identified from CSF specimens in 2 out of 9 culture negative patients, thus suggesting the usefulness of the PCR for the rapid diagnosis of CNS tuberculosis. The adenosine deaminase (ADA) levels in CSF may provide another diagnostic clue because they were elevated in 8 out of 10 cases. It is to be noted that there were three patients who developed clinical manifestations of CNS tuberculosis after the initiation of chemotherapy for pulmonary tuberculosis. In the last five cases, four-drug regimen which included PZA, was used with a good result. The success could be related to the addition of PZA which penetrates blood-brain barrier just as good as INH. Two patients died and one remains unconscious with severe neurological sequelae. The present study indicates that positive CSF culture, hydrocephalus and consciousness disturbance are important factors in determining poor prognosis of the CNS tuberculosis.

Twenty-four community residing elderly people in need of care, who were registered with the municipal welfare center in Miyagi Prefecture, Japan, and their principal caregivers participated in the study. The principal caregivers completed a self-administered questionnaire involving their demographic status, provided data on their utilization of formal services and completed the Center for Epidemiologic Studies Depression Scale (CES-D). The health visitors examined the activities of daily living (ADL) and mental status of these 24 elderly individuals. More than half the caregivers appeared to be depressed. The non-depressed caregivers used significantly more services than the depressed caregivers even after the caregivers' age was statistically controlled.

A 53-year-old woman was admitted to the hospital for investigation of an abnormal shadow in the middle lobe of the right lung on a chest X-ray film. The filling of most of the shadowed area with contrast media on a chest CT scan suggested a vascular lesion. Further investigation by intravenous digital subtraction angiography and color doppler sonography led to the diagnosis of pulmonary arteriovenous malformation. An abdominal CT scan suggested the presence of an arteriovenous malformation in the liver, and a bronchoscopic study revealed telangiectatic lesions on the laryngeal mucosa. The patient's father had died at the age of 61, due to intracranial bleeding, which suggested he might have had an arteriovenous malformation in the brain. The patient's daughter has a pulmonary arteriovenous malformation. This family of vascular malformation indicates that the patient had Osler-Weber-Rendu disease. Osler-Weber-Rendu disease is an autosomal-dominant inherited disorder that may give rise to arteriovenous malformations, mainly in the lungs and the brain. We found that color doppler sonography can be useful for the diagnosis of pleural-based pulmonary arteriovenous malformation.

Restriction-fragment-length polymorphism (RFLP) analysis was used to study one outbreak of reinfection pulmonary tuberculosis at a day-laborers' facility equipped with a sauna. The results were interpreted in conjunction with clinical and epidemiologic data. The DNA prove was derived from the insertion sequence IS 6110. A 63-year-old man who stayed at a day-laborers' facility for eight months was found to have advanced cavitary lung disease with sputum smears strongly positive for acid-fast bacilli. One year later a 46-year-old man staying at the same facility for 24 months was also found to have sputum-positive tuberculosis. The 46-year-old man had undergone treatment for tuberculosis 16 years previously and showed radiographic evidence of previous lung damage from tuberculosis. The second man had no tubercule bacilli in sputum when the 63-year-old man was found to have sputum-positive tuberculosis. The organisms isolated from these two men were both drug sensitive and had a similar RFLP pattern which suggests that 63-year-old man was the source of this outbreak and that pulmonary tuberculosis in the 46-year-old man was caused by exogenous reinfection. We conclude that exogenous reinfection may have been one pattern of tuberculosis transmission in this high-risk environment.

A 72-year-old man was exposed to the sarin gas attack in a Tokyo subway on March 20 th, 1995. After exposure, he noticed eye discomfort, chest tightness, headache and weakness of the lower limbs and oropharyngeal muscles. Despite these symptoms, he visited a hot spring on the same day with his family. On March 25 th, his muscle weakness progressed, and a low grade fever appeared. His muscle weakness disappeared 8 days after exposure to sarin, but respiratory failure rapidly developed, necessitating artificial ventilation within four day after hospitalization on March 28th. Chemotherapy with erythromycin, imipenem/cilastatin, and steroid pulse therapy was begu. PCR and culture of sputum collected by bronchofiberscopy were positive for Legionella pneumophila, serogroup I. His respiratory state improved, but subsequent infection with Pseudomonous aeruginosa. Enterobacter cloacae, and Candida tropicalis/glabrata caused his death 71 days after admission. Oropharyngeal muscle weakness caused by sarin-mediated cholinesterase inhibition was strongly suspected as the cause of hot spring water aspiration. Transbronchial lung biopsy revealed organizing pneumonia with fibrosis. Bronchoscopic findings included redness, edema and fragility of all visible areas of the airway, which was thought to be due to bronchitis caused by Legionellosis.

In current psychiatric therapy, two or more kinds of antipsychotic drugs are usually prescribed in Japan. However, there are few data on the therapeutic plasma concentrations of antipsychotic drugs or on the correlation between the daily dose and the plasma concentration, in cases where several antipsychotic drugs had been prescribed for each patient. We measured the therapeutic plasma concentrations of 9 antipsychotic drugs in 24 psychiatric inpatients during a 6-month period. They were treated with fixed dosages of antipsychotic drugs. Plasma samples were collected early in the morning once a month, and the concentrations of antipsychotic drugs were determined by gas chromatography with nitrogen phosphorus detection, high-performance liquid chromatography (HPLC) with fluorescence detection and HPLC with UV detection. The plasma levels of chlorpromazine, levomepromazine, thioridazine, haloperidol, bromperidol, zotepine, oxypertine, sulpiride and sultopride were 21.8-92.4, 31.7-156, 101-203, 16.4-56.2, 2.72-11.7, 13.6-84.0, 29.9-80.4, 70.1-1,120 and 35.7-2,990 ng/ml, respectively. A linear correlation between the daily dose and the plasma concentration was noted for sultopride, levomepromazine, sulpiride, haloperidol, chlorpromazine and zotepine.

A 29-year-old woman of the bronchial asthma was admitted to our hospital. Her asthmatic symptoms were refractory in spite of the administration of 30 mg of daily-oral prednisolone. During the asthma-attack, marked arterial oxygen desaturation was noted. So we doubted that she had obstructive sleep apnea complicated with obesity. Sleep Apnea Monitor revealed her nocturnal desaturation and frequent sleep apnea. To avoid the desaturation, we recommended her to keep prone position during the sleep. And both desaturation and asthmatic symptoms were dramatically improved. Nasal-CPAP also had been effective for them. These findings suggest that sleep apnea mediated oxygen desaturation may be one of the promotor of asthmatic symptoms.

A 76-year-old man was admitted to our hospital with a diffuse reticulo-nodular shadow on chest X-ray. He had no symptoms. Transbronchial lung biopsy specimens revealed alveolitis and small numbers of lymphocytes. Bronchoalveolar lavage fluid (BALF) analysis revealed an increased number of eosinophils. Few eosinophils were seen in the alveolar lumen on biopsy. The patient had no symptoms, and was discharged without therapy. He was followed as an outpatient. Dyspnea on effort gradually developed June 1995. The diffuse infiltrative shadows on chest CT worsened and the patient was again admitted. Laboratory data revealed an elevation of serum LDH. Tumor markers were negative. Desquamative interstitial pneumonia (DIP) was diagnosed on open lung biopsy. Corticosteroid therapy (1 mg/kg/day) was administered. After treatment with corticosteroid, chest CT findings and pulmonary function tests improved remarkably. DIP is less common in Japan than elsewhere. The characteristic findings of BALF taken from patients with DIP are still inperfectly characterized. Our patient exhibited an increased number of eosinophils. To the best of our knowledge, BALF findings were reported for six cases of DIP in Japan. In five out of the seven cases (including our case), BALF findings demonstrated an increased number of eosinophils. This finding may be one of the characteristic features in patients with DIP.

Alpha-fetoprotein (AFP) is a useful tumor marker for the diagnosis of hepatic and testicular tumors. Several cases of AFP-producing lung cancer have been reported. We present here a patient with AFP-producing primary lung carcinoma, which showed high values of serum AFP (100,000 ng/mL). The concanavalin A nonbinding fraction rate of AFP was 15%. Gross and microscopic features of the lung carcinoma bore a striking resemblance to those of hepatocellular carcinoma. According to the histologic classification of lung tumor, this case was large cell carcinoma with prominent hepatoid differentiation. Immunohistochemically, we detected AFP in the cytoplasm of the neoplastic cells. We also detected another useful tumor marker for the diagnosis of hepatocellular carcinoma, i.e., des-gamma-carboxy prothrombin (protein induced by vitamin K absence or the absence of antagonist-II [PIVKA-II]), in serum using an enzyme immunoassay and in tumor cells by immunohistochemical analysis.

A 25-year-old man was admitted to the hospital because of uncontrollable coughing and sputum production. He had been suffering from coughing and sputum production since he was 7 years old. He was given a diagnosis of bronchiectasis and persistent airway infection with Pseudomonas aeruginosa when he was 16 years old. One year of treatment with erythromycin and another year of treatment with roxithromycin were not effective. After he was referred to our hospital in 1993, he was given clarithromycin together with tosufloxacin for two years as an outpatient. The treatment was not very effective, but some prophylactic effect was seen with regard to prevention of acute exacerbations of Pseudomonas aeruginosa airway infection. Examination after admission revealed a high level of serum IgE (3703 U/ml), a strong skin reaction to aspergillus allergen, and marked central bronchiectasis in both upper lobes. He had no history of eosinophilia or of attacks of dyspnea. Our diagnosis was acute exacerbation of long-standing allergic bronchopulmonary aspergillosis and chronic airway infection. Treatment with oral prednisolone (30 mg per day) together with intravenous cefsulodin for three weeks resulted in marked relief symptoms and improvement in pulmonary function. The delay in correct diagnosis seems to have been caused by the lack of an obvious episode of asthma, and by the fact that the chronic productive coughing was thought to have been due to bronchiectasis, and to chronic bacterial infection. The characteristic bronchiectasis of this patient prompted us to examine the allergic reaction to aspergillus and let us to the correct diagnosis.