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In order to estimate the changes in the service for outpatients with hospital movement, patient flow investigation has been performed at both old and new hospitals. IC memory card was handed out to each outpatient, and timestamps and places were recorded on the card at the places that the patient have been by using card writers set at each department. By comparing with two results, old and new hospitals, patient-waiting time at payment counter was remarkably shortened because of the effect of order-entry system. However, there were few changes in stay time at clinical departments. From the results, it is found that optimization of booking system was required for improvement of patients flow at clinical departments.

Two opposite types of synaptic plasticity in the CA1 hippocampus, long-term potentiation (LTP) and long-term depression (LTD), require postsynaptic Ca2+ elevation. To explain these apparently contradictory phenomena, the current view assumes that a moderate postsynaptic increase in Ca2+ leads to LTD, whereas a large increase leads to LTP. No detailed study has so far been attempted to investigate whether the instantaneous Ca2+ elevation level differentially induces LTP or LTD. We therefore used low-frequency (1 Hz) stimulation of Schaffer collateral/commissural fibers in rat hippocampal slices, during a Mg2+-free period, as the conditioning stimulus to investigate this. This allowed low-frequency afferent stimulation to cause a postsynaptic Ca2+ influx because the voltage-dependent block of N-methyl-D-aspartate (NMDA) receptor-channels by Mg2+ was removed. When delivered during the Mg2+-free period, a single pulse, as well as 2-600 pulses, induced LTP that was occluded with tetanus-induced LTP. To decrease the Ca2+ influx, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors were completely blocked by the addition of 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) to the conditioning medium, in which 1 Hz afferent stimuli (1-600 pulses) induced less LTP and never induced LTD. To further reduce the Ca2+ influx, NMDA receptors were partially blocked with D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5). A small number of 1 Hz stimuli, however, never induced LTD. Only when the conditioning stimuli exceeded 200 pulses was LTD induced. The present findings provide definitive evidence that protracted conditioning is a prerequisite for the induction of LTD. Thus, not only the amplitude but also the duration of postsynaptic Ca2+ elevation could be essential factors for differentially inducing LTP or LTD.

JC virus (JCV) infection of oligodendrocytes causes demyelination in brains of patients with with progressive multifocal leukoencephalopathy (PML). Expansion of demyelination throughout the brain is not fully understood. The opportunity was taken to investigate the postmortem brain of a long surviving patient with PML for whom diagnosis was made 4 years before death based on pathological and virological findings of a brain biopsy. Four distinct regulatory sequences in the JCV genome were detected (designated as JW-1 to 4) from various regions of the necropsied brain. All regulatory sequences were rearranged forms that could be produced from the archetype by deletions and duplications. JW-1 and 2 shared some structural features not present in JW-3 and 4 and vice versa. JW-1 was distributed throughout the brain, whereas JW-2, 3, and 4 were restricted to only part of the brain. JW-1 and 2 had been detected in the initial brain biopsy 4 years earlier. These findings suggested that brain lesions in advanced stages were generated not only by expansion of the original variant (JW-1) of JCV but also by delayed growth of two other variants (JW-3 and 4).

While stenting improves the long-term angiographic outcomes of successfully recanalized chronic coronary total occlusions (CTO), the restenosis rate still remains high. The massive plaque burden in CTO is considered to be one of the causes of in-stent restenosis.We examined the pre-stent plaque debulking strategy with high-speed rotational atherectomy (RA) for 50 CTO (Thrombolysis in Myocardial Infarction flow grade 0; estimated occlusive duration, 3 months). Angiographic follow-up results were compared to those of 120 consecutive CTO recanalized with primary stenting in which RA could be indicated retrospectively. Angiographic restenosis was defined as diameter stenosis50% at 6-month follow-up.RA could be performed safely in all lesions without any major complications. Adjunctive ballooning and stenting could be performed without high-pressure dilatation (8.4 +/- 1.7 atmospheres). Follow-up angiography was performed in 48 lesions 184 +/- 61 days after the procedure. There were no significant differences in baseline characteristics between the two groups; however, the implanted stent type was different. Quantitative coronary angiography revealed that diameter stenosis was smaller at follow-up (36.2 +/- 20.0% versus 52.2 +/- 26.7%; p = 0.0003) as well as post-procedure (7.8 +/- 11.5% versus 17.8 +/- 13.6%; p0.0001) compared with the control group. Angiographic restenosis was also significantly reduced (29.2% versus 52.5%; p = 0.0061).RA is a safe procedure for plaque debulking of CTO in selected cases. Plaque debulking of CTO facilitates subsequent stent expansion and may reduce the restenosis rate.

We report an improved mitral exposure technique for mitral valve re-operation. Left mediastinal pleurotomy through a median sternotomy achieves rotation of the heart and excellent exposure of the mitral valve allowing the apex to drop posteriorly. We employed this technique in redo mitral valve surgeries for over a 3-year period. This minimal adhesiotomy method is technically simple, safe and time-saving.

A 64-year-old man was hospitalized for productive cough and dyspnea. Both chest radiographs and CT scans showed areas of ground-glass opacity in the middle and lower lung fields on both sides. The BAL and TBLB findings were compatible with hypersensitivity pneumonitis. The serum was negative for antibodies against Trichosporon species, and the result of a lymphocyte stimulating test for administered drugs including a Chinese medicine was also negative. A humidifier was suspected as the cause because it had been used for more than 10 years in the factory where the patient had been working. An inhalation test using the humidifier fluid successfully provoked dyspnea, fever and fine crackle, and laboratory tests demonstrated hypoxemia, reduction in vital capacity and the elevation of CRP. Agar gel diffusion using the patient's serum showed a precipitating line against Cephalosporium acremonium, but this line did not fuse with any precipitating line formed between the humidifier fluid and the serum, indicating that no Cephalosporium was Present in the humidifier fluid. Since a high level of beta-D glucan was detected in the humidifier fluid, an unidentified fungus was suspected to be the antigen.

Multilayer reflectors and position sensitive detectors have been developed in constructing imaging optical systems in the 45–300 A region. Molybdenum‐silicon (2d=140 A, N=20) and nickel–carbon (2d=100 A, N=20) multilayers were deposited on a spherical mirror (25 cm in diameter) for the normal incidence and on a segment of paraboloidal mirror (20 cm×10 cm) for 30° grazing incidence. Their optical characteristics were evaluated by using characteristic x rays and monochromatized synchrotron radiation in the 45–300 A region. A position sensitive detector is made of a tandem microchannel plate (MCP) with a CsI photocathode and resistive plate, which is placed at the focal plane of each mirror. The detection efficiency and position resolution were measured by using characteristic x rays of CKα and monochromatized synchrotron radiation in the 45–200 A region.

We report a case of non-functioning retroperitoneal paraganglioma detected incidentally by health examination in a 60-year-old female without any clinical manifestation. She was admitted to our hospital for the purpose of evaluation of a renal mass detected by ultrasound sonography. Computed tomography, magnetic resonance imaging and angiography revealed the heterogeneously-enhanced 10 x 10 cm mass in the left retroperitoneal space without any distant metastasis. It was suspected to be a renal cell carcinoma. All laboratory data, including those from endocrinological examinations, were within normal ranges. Radical nephrectomy was performed to resect en bloc the mass and the left kidney. The pathological and immunohistochemical examinations of the mass which was completely separated from the kidney and the adrenal gland, showed characteristic features of paraganglioma with vascular and capsular invasion, with a final clinical diagnosis of the pathologically-malignant non-functioning paraganglioma occurring between the left kidney and the adrenal gland.

We have investigated the thermal unfolding of bovine alpha-lactalbumin by means of circular dichroism spectroscopy in the far- and near-ultraviolet regions, and shown that the native alpha-lactalbumin undergoes heat and cold denaturation. The guanidine hydrochloride-induced unfolding of alpha-lactalbumin was also investigated by circular dichroism spectroscopy at various temperatures from 261 to 318 K. It is shown that the population of the molten globule state is strongly dependent on temperature and that the molten globule state does not accumulate during the guanidine hydrochloride-induced unfolding transition at 261 K. Our results indicate that the molten globule state of alpha-lactalbumin undergoes cold denaturation as the native alpha-lactalbumin does, and that the heat capacity change of unfolding from the molten globule to the unfolded state is positive and significant. The present results further support the idea that the molten globule and the unfolded states do not belong to the same thermodynamic state, and that the native, molten globule and unfolded states are sufficient for interpreting the guanidine hydrochloride-induced unfolding behavior of alpha-lactalbumin.

Recent studies have shown that nitric oxide interacts with superoxide to form peroxynitrite, a potent oxidant that modifies cellular proteins producing 3-L-nitrotyrosine (N-Tyr). This study was designed to evaluate N-Tyr quantitatively with high-performance liquid chromatography (HPLC) during cardiac allograft rejection.Rat transplanted hearts (allogeneic or syngeneic grafts) were examined with HPLC analysis, immunohistochemistry for N-Tyr, and histological studies on 0, 1, 3, and 7 days after transplantation.No histological rejection was found in syngeneic grafts, or day 0 or 1 allografts. HPLC demonstrated that N-Tyr in allografts increased on day 1 and continued to increase through day 7, while N-Tyr was not detected in any syngeneic grafts. Immunostaining of the allografts did not show N-Tyr on day 1.These results demonstrate that N-Tyr shows a time-dependent accumulation in cardiac allografts during acute rejection. N-Tyr detection using HPLC may be an useful maker for early diagnosis of acute rejection before pathological rejection occurs.

Many protocol studies have shown that low dose 6-mercaptopurine (6MP) in maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL) can be utilized to cure the disease. Mitotic or reproductive cell death has been recognized after G2 arrest when cells are treated with antitumor agents. The precise mechanism of mode of action of 6MP still remains unclear. We found delayed cytotoxic effect of 6MP in P388 murine leukemic cells. Morphological study showed that 6MP induced delayed death was characterized by an enlargement of cell size and multinucleated nuclei. Agarose gel electrophoresis of fragmented DNA from cells treated with 6MP showed the typical ladder pattern. These findings were compatible with mitotic death. Our results make us hypothesize that the delayed cytotoxicity of 6MP is one of the drug induced mitotic deaths caused by DNA damage due to incorporation of 6-thioguanine (6TG) into DNA as thioguanine nucleotide (TGN). Mitotic death may be a mechanism for killing the cycling cells from residual leukemic cells in G0 or long G1 phases in the treatment of childhood ALL.

A 26-year-old man was admitted to our hospital complaining of exertional dyspnea. Chest x-ray films disclosed reticulonodular shadows predominantly in the upper fields of both lungs, but no apical cap. Lung biopsy specimens obtained from the upper lobe by video-assisted thoracoscopy revealed subpleural elasto-fibrosis. Also, specimens obtained from the lower lobes disclosed micro-honeycombing due to peri-lobular fibrosis resembling usual interstitial pneumonia. Although pneumothorax occurred repeatedly, the lungs reinflated on each occasion without artificial intervention. Similar radiographic findings had been obtained on the patient's father, who died of idiopathic pulmonary fibrosis at the age of 56. Idiopathic pulmonary upper lobe fibrosis was conclusively diagnosed because the patient exhibited most of the features originally described by Amitani et al.

Human thrombopoietin (TPO) is a haemopoietic growth factor that is essential for the growth and development of megakaryocytes. However, c-Mpl, the TPO receptor, has been detected in human leukaemic cell lines with a myelomonocytic phenotype. These results raise the possibility that dendritic cells (DC), a putative myeloid lineage cell, may also express c-Mpl and respond to TPO. In haemopoietic stem cell transplantation, DC could induce graft-versus-host disease by its strong antigen-presenting capacity. In this study we have examined the effect of TPO on differentiation and the antigen-presenting capacity of DC. To differentiate DC, cord blood CD34+ cells were cultured in the presence of a cytokine cocktail either in serum-free medium or RPMI1640 containing 10% fetal bovine serum. Flow cytometric analysis and immunocytochemical staining demonstrated that c-Mpl was expressed on DC. Furthermore, the expression of c-Mpl mRNA was detected in DC by RNase protection assay. However, when TPO was added to the culture system there were no significant changes in the differentiation and mixed leucocyte-stimulating capacity of DC. These findings suggest that TPO may be administered following cord blood transplantation without significant augmentation of antigen presentation mediated by DC.

The synthesis and biological activity of a novel series of 2-alkyl-4-pyrrolidinylthio-beta-methylcarbapenems containing a variety of cationic heteroaromatic substituents is described. As a result of these studies, we uncovered a relationship between in vitro antibacterial activity and the length of the alkyl spacer part, and discovered FR20950 (1c), containing a two methylene spacer moiety and an imidazolio group, which possesses a balanced spectrum of antibacterial activity, including Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, FR20950 exhibited excellent urinary recovery, and comparable stability against renal dehydropeptidase-I (DHP-I) to Biapenem. DHP-I stability could be improved by introduction of a substituent on to the imidazole ring.

Granisetron has been used widely for the prevention and treatment of nausea and vomiting associated with anticancer drugs in adult patients with cancer. This multi-center open study was conducted to study the efficacy, safety and usefulness of granisetron in children with cancer. Among 166 evaluable patients, the efficacy rate (percentage of "remarkably effective" or "effective") was 84.9% and the usefulness rate (percentage of "extremely useful" or "useful") was 87.3%. No serious adverse effects were observed. As granisetron 40 micrograms/kg had an excellent antiemetic effect and a high degree of safety against nausea and vomiting associated with anticancer drugs, it was shown to be useful for children with cancer.

Human neuroblastoma (NB) cell lines have at least three morphological appearance of neuroblastic (N-type), substrate-adhessive (S-type) and intermediate(I) cells. Our previous study revealed S-type cells expressed alpha-smooth muscle actin, desmin and/or basic-calponin, indicating the plausible smooth muscle cell characteristics of S-type cells. In this study, a new human NB cell line, MP-N-MS, was established from bone marrow metastasis of a one year and six-month old girl with advanced NB, originating from right adrenal gland. Morphology of this cell line is composed of S-type cells. MP-N-MS was identified as a NB cell line by surface membrane antigen analysis and MYCN gene amplification. EWS-FLI1 and EWS-ERG chimeric products, observed in Ewing family tumors, were not detected by RT-PCR (reverse transcriptase-polymerase chain reaction). In cytoskeletal protein analysis, alpha-smooth muscle actin and basic calponin of smooth muscle cell markers were detected. Furthermore, smooth myosin of SM1 isoform was identified in MP-N-MS cell line by immunofluorescence, Western blot and RT-PCR, whereas smooth myosin of SM2 was detected by RT-PCR. MP-N-MS is the first cell line, showing SM1 and SM2 isoforms. The presence of smooth muscle myosin of SM1 and SM2 isoforms in MP-N-MS demonstrated the mature smooth muscle phenotype of this NB cell line, and the ability of NB cells to differentiate into smooth muscle cell.

This study was aimed to evaluate the usefulness and feasibility of extracorporeal shock wave lithotripsy (ESWL) performed in elderly patients. ESWL by Triptor X-1 was used to treat 530 patients with upper urinary tract stones from 1991 to 1998. Sixty one (11.5%) of them were aged 70 years and older. The results of ESWL treatment in this elderly group were compared retrospectively with those in 122 patients aged from 20 to 39 and 243 patients aged from 40 to 59. Although the elderly had a higher incidence of preoperative risk factors, the postoperative complication rates were similar among all groups. The stone-free rate and the success rate at one month in the elderly group were 67.2% and 92.5%, respectively, which were similar to those in the younger groups. These results suggested that ESWL offered a safe and effective means of treating upper urinary tract stones in elderly patients.

We report a Japanese family with ataxia with isolated vitamin E deficiency (AVED). Gene analysis revealed a single nucleotide substitution of T to C at nucleotide position 2 in the alpha-tocopherol transfer protein gene (TTPA). This substitution abolishes the start codon. The proband and his affected sister were homozygous for this mutation, and their serum alpha-tocopherol concentrations were remarkably reduced. Relations between the mutations and clinical features are discussed.

A 45-year-old woman was admitted to our department for a tumor shadow in the right lung on chest rentogenogram and chest CT. Detailed examination led to the diagnosis of simultaneous lung cancer and ovarian cancer. No abnormality was found in the liver. Serum AFP level was 113.8 ng/ml preoperatively, but deceased upper lobectomy of the right lung to 11.4 ng/ml on the 15th day postoperatively. Immunohistochemical study revealed positive staining of carcinoma cells with anti AFP serum.

We report a rare case of a 39-year-old man with type A aortic dissection involving a right-sided aortic arch with the symptom of vascular ring. Computed tomography scanning and angiography were performed to define the extent of the dissection and the anatomy of the branching vessels. The ascending aorta was replaced through a median sternotomy and right thoracotomy using a hypothermic cardiopulmonary bypass associated with selective cerebral perfusion and partial circulatory arrest, and his symptom of vascular ring disappeared postoperatively.

Of 40 Wilms tumors with chromosome abnormalities, 6 were hypodiploid, 10 were pseudodiploid, 7 were hyperdiploid with 47 to 49 chromosomes, and 17 were hyperdiploid with 50 or more chromosomes, mostly including +12. WT1 deletions/mutations were found in one hypodiploid, eight pseudodiploid, and one hyperdiploid (47-49 chromosomes) tumor, but in none of the hyperdiploid (or =50 chromosomes) tumors. Of the 10 tumors with WT1 abnormalities, 6 had a homozygous WT1 deletion, 1 had a nonsense WT1 mutation and loss of heterozygosity at 11p, 1 had an intragenic hemizygous WT1 deletion without detectable WT1 mutation, and 2, which occurred in Wilms tumor-aniridia-genitourinary abnormalities-mental retardation syndrome patients, had a hemizygous deletion and a missense or frameshift mutation of WT1. Six of the nine tumors with homozygous or hemizygous WT1 deletions had chromosome aberrations involving chromosome band 11p13 in one of the two chromosomes 11. While one hypodiploid and one pseudodiploid patient died of the disease, and one hyperdiploid (47-49 chromosomes) patient was alive in nonremission, all hyperdiploid (or =50 chromosomes) patients had no evidence of disease at the last follow-up. Our data show that chromosome aberrations are closely correlated to WT1 abnormalities and suggest that hyperdiploid (or =50 chromosomes) Wilms tumors may be characterized by the absence of WT1 abnormalities and possibly also by a favorable prognosis.

It has been reported that aclarubicin inhibits etoposide (VP-16) induced cytotoxicity in human lung cancer cell lines (1, 2). However, it still remains unclear how aclarubicin (ACR) inhibits etoposide-induced cytotoxicity. We report here that the combination of ACR and VP-16 showed antagonistic cytotoxic effect in P388 murine leukemic cells. DNA unwinding assay showed that 1000 ng/ml ACR significantly reduced VP-16 induced early DNA double strand(ds) breaks compared to that of VP-16 alone at a concentration of 10 microM. However, ACR did not inhibit VP-16 induced early DNA double strand breaks at a concentration of 100 ng/ml, a clinically achievable concentration. Furthermore, DNA repair occurred within two hours after removing VP-16 even if ACR was co-cultured at concentrations of 100 and 1000 ng/ml. DNA agarose gel electrophoresis and detection of sub-G1 fraction by flowcytometer showed that 100 ng/ml of ACR inhibited VP-16 induced DNA ladder formation and formation of sub-G1 fraction. Radioactive precursor incorporation studies showed that VP-16 inhibited DNA synthesis rather than RNA synthesis. On the other hand, ACR selectively inhibited RNA synthesis at a concentration of 100 ng/ml. The VP-16 induced increment of [3H]-L-leucine uptake was canceled by addition of 100 ng/ml of ACR. These data suggest that ACR inhibited VP-16 induced apoptosis by the inhibition of RNA synthesis along with protein synthesis, but not early DNA double strand breaks and DNA repair at a concentration of 100 ng/ml in P388 murine leukemic cells.

The mass screening (MS) of neuroblastoma has been undertaken in Japan by measuring urinary catecholamine metabolites in infants at the age of 6 months. To clarify the biological characteristics of MS-positive (MS+) tumors in infants and MS-negative (MS-)/late-presenting tumors in young children, metaphase cytogenetic and/or interphase 2-color FISH analyses using terminal 1p and pericentromeric 1q probes were performed on 246 (186 MS+ and 60 MS-) patients with neuroblastomas. The 246 tumors were classified into 4 groups on the basis of the constitution of chromosome 1; 22 tumors had disomy 1 with no 1p deletion (Dis1Norm1p); 41 tumors had disomy 1 or tetrasomy 1, all with the 1p deletion (Dis1Del1p); 164 tumors had trisomy 1, pentasomy 1, or a mixed population of cells with trisomy 1 and cells with tetrasomy 1, none with 1p deletion (Tris1Norm1p); 19 tumors with the same copy numbers of chromosome 1 as the Tris1Norm1p group, had 1p deletion (Tris1Del1p). mycn amplification was absent in the Dis1Norm1p and Tris1Del1p groups, frequent in the Dis1Del1p group (24/41), and rare in the Tris1Norm1p group (3/164) (p0.0001). Event-free survival at 5 years was lowest [19.5%; 95% confidence interval (CI), 5.1-33.9] in the Dis1Del1p group, highest in the Tris1Norm1p (96.3%; 95% CI, 93.5-99.2) and Tris1Del1p (94.7%; 95% CI, 84.7-104.8) groups, and intermediate but varied (54.5%; 95% CI, 33.7-75.4) in the Dis1Norm1p group (p0.0001). Of the MS+ tumors, 90% were Tris1Norm1p or Tris1Del1p, and 55% of the MS- tumors were Dis1Del1p. The finding that the Dis1Del1p tumors were frequent in MS- but not in MS+ tumors suggests the limited efficacy of the MS program into reducing mortality from neuroblastoma.

The types of HLA-A, -B and -DRB1 genes were studied in 146 Japanese patients with multiple sclerosis (MS) using polymerase chain reaction-sequence-specific oligonucleotide probe analysis. Fifty-seven patients who displayed selective clinical involvement of the optic nerve and spinal cord were classified as having Asian type MS. The other 89 patients had disseminated central nervous system involvement and were classified as having Western type MS. The frequency of HLA-B*5101 was increased in both types of MS patients compared with controls. The frequency of HLA-DRB1*1501 was increased in Western type MS and the frequency of HLA-DRB1*0802 was increased in Asian type MS compared to controls. After correction of P values, the association of Western type MS patients with HLA-DRB1*1501 was statistically significant (Pc=0.0003) whereas other HLA alleles showed no significant association. These results suggest that HLA class I (HLA-A and -B) alleles may not contribute to a strong susceptibility to MS in Japanese compared to HLA class II (HLA-DRB1) alleles.

A 28 year old man with no underlying disease developed a cavity and multiple nodules in the lung from which Corynebacterium equi was isolated. He experimented with organic solvents and microorganisms including Corynebacterium species for several years. Computed tomography of his pulmonary lesions revealed that these nodules were related to the bronchial tree. Histologically, the lesions were compatible with nonspecific inflammatory changes. The clinician must suspect the pulmonary infections with Corynebacterium species even if the patient has no underlying disease.

Characterizations of multilayer reflectors were performed in the wavelength range 3–10 nm using synchrotron radiation. Layer spacing of the multilayers, which were fabricated by the electron beam vapour deposition method, exists in the range 6–10 nm. Evaluation of multilayers was carried out by measuring the reflectivity, the wavelength resolution and the Bragg angle on the beam line for radiometric calibration (BL5B) in the UVSOR facility. The incident photon beam was monochromatized by a plane grating monochrometer. Reflectivity was measured for both s and p components using a demountable rotational stage. The peak reflectivity was found to be in the range of 1–10%, and the reflectivities of both polarization components showed the most pronounced difference at an incidence angle of 45°, which proves that the multilayer is also useful as an X-ray polarimeter.

The components of the gyration tensor of the enzyme lysozyme were measured by using the HAUP method: g11 = -0.90 x 10(-5) and g33 = 1.05 x 10(-5) at 303.4 K and a wavelength of 4880 A. The optical rotatory powers along the a and c axes in the same conditions were calculated: rho a = -21.3 and rho c = -24.8 degrees cm-1. The optically active property of lysozyme is strange in that, although it contains a considerable quantity of alpha-helices (about 30%), the rotatory powers are unexpectedly small in magnitude, one order of magnitude less than those of quartz and with very large anisotropy. A conceptual consideration of this phenomenon is given. In order to assess the difference between the structures in both crystalline and solution states, the chirality index r was calculated to be 0.16. This value indicates that the structural change of lysozyme from the solution into the crystalline state is expressed by an increase of 19% in optical activity. From the NMR results [Smith et al. (1993), J. Mol. Biol. 229, 930-944], it is anticipated that the r value reflects the increased constraint in atomic motion in the side chains of exposed amino acid residues in the crystalline state.

Several reports have shown that an increase in T-cell receptor gamma/delta-positive T-cells (gamma delta T-cells) have been observed following bone marrow transplantation. gamma delta T-cells expanded from peripheral blood mononuclear cells from normal volunteers were used to investigate the function of gamma delta T-cells in vitro. Peripheral blood mononuclear cells were cultured with synthetic ligand of gamma delta T-cells, monoethyl phosphates (MEP), for 7 days. MEP specifically expanded gamma delta T-cells. Expanded gamma delta T-cells from subject "B" were added to an A anti-B or A anti-C mixed lymphocyte culture (MLC) containing responder cells from subject "A" and irradiated stimulator cells from subjects "B" or "C". The cultures were harvested on day 6 and tested for cytotoxicity against stimulator-type Con A blasts. gamma delta T-cells from subject "B" specifically inhibit generation of allospecific cytotoxic T lymphocytes (CTL) in A anti-B MLC. The results indicate that gamma delta T-cells exhibit veto-type suppression of alloreaction. If the current experiments are also applicable in vivo, gamma delta T-cells originating from the donor after bone marrow transplantation may inhibit graft rejection by suppressing recipient anti-donor reactivity. gamma delta T-cells may be involved in the suppression of allogeneic reaction in vivo following allogeneic bone marrow transplantation.

To evaluate the reproducibility of the Ultrafast CT (UFCT) scoring system and assess its usefulness in monitoring clinical severity in infants with bronchopulmonary dysplasia (BPD).UFCT scoring was done in 22 infants (15 boys and 7 girls aged 1 to 37 months) with BPD. A total of 258 lung fields were evaluated for the presence of hyperaeration, linear opacities, triangular subpleural opacities, and bronchovascular bundle distortion or thickening, and UFCT scores were given. Intraobserver and interobserver agreement and reproducibility of UFCT scores were statistically analyzed. In 12 patients, UFCT scores were linearly correlated with clinical severity scores based on respiratory dysfunction and complexity of care."Hyperaeration," which was the most frequent (18 of 22, 81.8%) finding, showed high concordance (kappa = 0.73, p0.001, kappa = 0.59, p0.001), and its UFCT scores significantly correlated with intraobserver and interobserver analyses (r = 0.94, p0.001, r = 0.82, p0.001, respectively). UFCT scores for hyperaeration significantly correlated with clinical scores (r = 0.75, p0.01), whereas those for the others did not.UFCT is useful for assessing BPD. Hyperaeration was the most common and reproducible finding, and its extent significantly correlated with clinical severity.

Eleven patients with symptomatic intracranial atherosclerotic stenotic lesions underwent percutaneous transluminal angioplasty (PTA). Seven patients had stenosis in M1 segment of the middle cerebral artery (MCA), two in the cavernous internal carotid artery, one in M2 segment of the MCA and one in the P2 segment of the posterior cerebral artery. Initial successful dilatation (less than 50% residual stenosis) was obtained in nine patients (81.8%). Permanent neurological deficit related to PTA was seen in one patient and transient symptoms were observed in two. Re-stenosis was revealed in two cases (18.2%) in the early follow-up period. All patients with successful dilatation and without re-stenosis never had TIA or stroke after PTA. Intracranial PTA is an effective procedure, but several problems remain to be solved.

We report a simultaneously operated case of a 68-year-old man with lung cancer accompanied with aortic arch aneurysm. Preoperative staging CT for lung cancer incidentally demonstrated another lesion in the para-aortic arch area, which was suspected to be rather a pleural or intrapulmonary lesion by enhanced CT and MRI. However, this lesion was intraoperatively diagnosed as a cystic small sized-aneurysm. After a left upper lobectomy with lymph node dissection for lung adenocarcinoma (T2N0) was performed, this aneurysm was tightly wrapped using PTFE felt during the course of one operation. The difficulty of peroperative diagnosis by CT and MRI for small sized-aneurysm is discussed, and surgical stragety for lung cancer accompanied with such an aortic aneurysm is also commented.

Cytogenetic and molecular-genetic characteristics in peripheral T cell lymphoma (PTL) have not been well defined, except for those in adult T cell leukemia/lymphoma (ATL/L). Translocations and inversions involving a chromosome band 14q32 were extremely common abnormalities reported in PTL and ATL/L. We studied the involvement of TCL1, a recently isolated gene located in 14q32.1, in tumor tissues from 20 patients with PTL including three with 14q32 translocations by two color fluorescent in situ hybridization (FISH) using two cosmid probes flanking the TCL1 gene. The two cosmid signals were separated in none of them, but much increased in number in one tumor without 14q32 translocation, indicating that the TCL1 genomic region was amplified in this tumor. Reverse transcription-polymerase chain reaction (RT-PCR), however, failed to detect the TCL1 transcript in the tumor. These findings suggest that an oncogene other than TCL1 may be located in 14q32.1, and its amplification may be involved in the neoplastic process of PTL.

The concentration of ECP in serum has been proposed as a marker of airway inflammation in asthma. However, its clinical significance is still to be determined.This study was performed to determine whether concentration of ECP in serum reflects clinical status in asthma and can serve as a predictive parameter.Cross-sectional analysis was performed in 28 children with asthma. A total of 91 blood samples was obtained to determine levels of ECP in serum and eosinophil counts. Forced expiratory volume in 1 s was also determined at the time of the sampling. Data were analysed on the basis of asthma symptoms in the 4 weeks before and the 4 weeks after sampling.Serum levels of ECP were significantly lower in patients who had been asymptomatic for 3 or 4 weeks before sampling than in patients who had been symptomatic or asymptomatic for only 1 or 2 weeks. In the former group, serum levels of ECP were higher when patients became symptomatic after sampling than when they remained stable, a finding that suggests that serum levels of ECP may have a predictive value in certain situations. Although the concentration of ECP in serum was not proved to be predictive in the latter symptomatic group, the concentration of ECP was significantly lower when measured again 4 weeks later when the patients' symptoms had resolved. In contrast, levels of ECP were unchanged when patients remained symptomatic, a finding that suggests serum levels of ECP may reflect the clinical response to therapy.Serum ECP may be a useful marker for monitoring and predicting the clinical course in asthma.

By in situ hybridization (ISH) method using digoxygenin (DIG)-labeled RNA probe, we proved the localization and replication of hepatitis C virus (HCV) RNA not only in the hepatocytes but also in the lymphocytes of the 52 liver tissues of chronic hepatitis C. We classified the staining patterns into four groups. The pattern of signal distribution significantly correlated with serum alanine aminotransferase (ALT) level, quantity of serum HCV RNA just before liver biopsy, histological grade of inflammatory activity, and stage of fibrosis by Spearman rank correlation. Moreover, we investigated the relation between the signals in the hepatocytes or lymphocytes and the effectiveness of interferon (IFN) therapy. Therefore, we suggest that ISH is a useful tool to evaluate the activity of chronic hepatitis C associated with serological and histopathological changes and is an important marker to assess the effectiveness of IFN treatment.

We examined whether paracrine factors produced by prostate cancer cells can modulate bone metabolism in proportion to the volume of cancer cells in bone metastasis. Endocrine factors produced by prostate cancer cells affect both phosphate and 1,25-dihydroxyvitamin D metabolisms. Levels of urine pyridinoline (U-Pyr) excretion and serum carboxy-terminal propeptide of type 1 procollagen (P1CP) in patients with bone metastasis were significantly higher than those in patients without bone metastasis (P0.05). In patients with bone metastasis (n = 17), serum prostate-specific antigen (PSA) levels were significantly correlated with the levels of U-Pyr and urine deoxypyridinoline (U-dPyr) excretion, serum cross-linked carboxyterminal telopeptide of type 1 collagen (1CTP), and P1CP levels (p0.05). However, serum PSA levels were not correlated with U-Pyr, U-dPyr excretions, serum 1CTP and P1CP levels in patients without bone metastasis. Therefore, prostate cancer cells appear to have some paracrine effects on bone cells. In controls (n = 15), serum 1,25-dihydroxyvitamin D levels (1,25-(OH)2D) were inversely correlated with serum phosphorus levels (P0.01). In prostate cancer patients with bone metastasis, the ability to regulate the serum 1,25-(OH)2D levels in response to serum phosphorus levels is lost. These results suggest that endocrine factors produced by prostate cancer cells disturb the regulation of serum 1,25-(OH)2D in response to serum phosphorus levels.

We investigated the correlation between tumor angiogenesis and prognosis of T1N0M0 lung adenocarcinoma.Forty two specimens resected from patients with T1NOM0 lung adenocarcinoma were investigated by immunohistochemical staining with a monoclonal antibody to CD31. The relationship between microvessel count, clinicopathologic factors and prognosis was studied.The microvessel count was significantly higher in cases with vessel invasions than in those without. Univariate analysis showed that microvessel count was related to poorer prognosis. In patients with a high microvessel count (or = 38), prognosis was significantly poorer than in those with a low count (38). Multivariate analysis indicated that the microvessel count and mitosis are prognostic factors in patients with lung cancer, and that the microvessel count is a more important factor than mitosis.Microvessel count may be a major prognostic factor and a useful tool to predict recurrence in patients with T1N0M0 lung adenocarcinoma.

In 1982, the Fourth International Workshop on Chromosomes in Leukemia reviewed data prospectively collected on 716 patients with acute myeloid leukemia (AML) diagnosed between 1980 and 1982. The present study examined the extended follow-up on these patients.The analyses included cytogenetic and clinical data, with a median follow-up of 14.7 years, from 54 patients with treatment-associated AML and 628 with de novo AML. Of these patients, 291 received induction therapy that would be considered standard by today's criteria; no patient received high-dose cytarabine (HiDAC) intensification.Among the patients with treatment-associated AML, the only long-term survivor in retrospect appears to have had de novo AML. Among the patients with de novo AML, achievement of complete remission and survival varied significantly based on cytogenetic classification among all 628 patients as well as among those who did and did not receive standard induction therapy. The remission rate and survival were significantly better with standard induction therapy for patients with t(15;17) and normal cytogenetics. Multivariate analyses showed that karyotype was an independent predictor of survival for all patients and those receiving standard induction therapy. Only 8.9% of patients were alive 5 years following diagnosis, but 5 years of continuous remission was synonymous with cure. Even among 5-year survivors who had suffered a previous relapse, 41% appeared to be cured. Survival among patients in continuous remission foror = 10 years varied significantly by cytogenetic classification. In the absence of HiDAC intensification, no complete responders with t(8;21) and only 7% with normal cytogenetics survived continuously 10 years disease free.Cure of AML following specific therapies must be evaluated in the context of cytogenetics. A meta-analysis incorporating cytogenetic data is indicated for patients withor = 10 years of follow-up.

Intimal lesions observed in the coronary arteries (CAs) of patients who have suffered episodes of Kawasaki disease (KD) raise concern about the premature development of arteriosclerosis. Accordingly, we investigated endothelial function in the epicardial and resistance CAs after KD during long-term observation.We assessed the responses of left epicardial and resistance CAs to serial intracoronary infusions of acetylcholine (final concentrations, 0.1 and 1 micromol/L) and nitroglycerin in subjects by using quantitative angiography and a Doppler flow wire system. Three age-matched groups were evaluated: 8 control subjects (group 1), 10 KD patients with normal left CA from the onset (group 2), and 8 KD patients with a persistent or regressed aneurysm in the left anterior descending CA (LAD) (group 3). Acetylcholine (1 micromol/L) changed the LAD area to 114.0+/-2.6%, 72.7+/-3.9% (P.05 versus group 1), and 88.9+/-4.3% (P.05 versus groups 1 and 2) of baseline in groups 1, 2, and 3, respectively, with a similar degree of increased coronary blood flow in each group. Nitroglycerin increased the LAD area to 143.5+/-7.7%, 132.3+/-1.9%, and 120.8+/-5.6% (P.05 versus group 1), respectively.Results demonstrate a persistent endothelial dysfunction in the epicardial but not resistance CAs in patients after KD and enhanced stiffness of persistent or regressed aneurysms. The concern over early arteriosclerosis warrants the surveillance of KD patients from childhood to adulthood.

We describe a patient with gastric cancer and membranous glomerulonephritis (MGN). The patient, a 61-year-old male, was admitted to our Hospital in May, 1996, because of proteinuria and hyperlipidemia persisting for a year. Laboratory examination filled the criteria of nephrotic syndrome and renal biopsy revealed MGN of stage II. Prednisolone therapy (40 mg/day p.o.) was started, followed by a gradual decrease in proteinuria from 4.5 g/day to 0.1 g/day. Endoscopic examination was performed because of stomach-ache revealed advanced gastric cancer of Borrmann 4. Desiring for a conservative therapy, he was discharged and moved to a hospice. In literature review, MGN is the most frequent lesion among various glomerular diseases associated with malignancy, such as the lung, stomach, and colon, particularly at an elderly ages, and sometimes antedates the detection of malignancy, as in the present case. In several cases with MGN, immune-complexes composed of tumor antigens, such as carcino-embryonic antigen, and antibodies have been reported to deposit in basement membrane of glomeruli, causing MGN. In the renal and gastric cancer tissues of the present case, the presence of three novel tumor-associated antigens, Span-1, Thomsen-Friedenreich antigen (T antigen) and F1 alpha antigen, was examined, using a immuno-peroxidase method. Although none of these three antigens were immuno-stained in the renal tissue, clinical course and literature review suggest that MGN in this patient seems to be associated with gastric cancer, which may have produced MGN-causing tumor antigens other than the three antigens. It should be emphasized that malignancy should be carefully and routinely examined in patients with MGN, particularly at elderly ages.

A 47-year-old woman was admitted on August 4th, 1995, because of edema of the lower extremities. She had been suffering from RA for about 20 years and underwent total knee-replacements 5 years previously. On admission, nephrotic syndrome and rapidly progressive glomerulonephritis had developed in association with ileus, melena, diarrhea, dyspnea and hemoptysis. She showed a high titer of serum rheumatoid factor (357.0 IU/ml) and amyloid A protein (83.9 micrograms/ml) with positive antinuclear antibodies (homogeneous and speckled patterns). However, anti-neutrophil cytoplasmic autoantibody (ELISA), immune complexes and anti-glomerular basement membrane antibody (ELISA) were negative. Renal biopsy showed microscopic PN overlapping A-type positive amyloidosis. Although the maintenance of hemodialysis was necessary, aggressive immunosuppressive therapy with steroid pulse therapy and frequent plasma exchange provided a rapid improvement of systemic symptoms possibly due to vasculitis. We suggested that in this case, massive necrotizing crescentic glomerulonephritis with systemic arteritis developed on the basis of secondary amyloidosis due to rheumatoid arthritis. In such a case, even if various serum autoantibodies and immune complexes were negative, plasma exchange was suggested to be effective to remove not only pathogenic autoantibodies but also various serum inflammatory cytokines which may be related with severe vasculitis and glomerulitis, in addition to aggressive steroid therapy which may suppress the invasion of inflammatory cells producing these cytokines.

Phase II study of combination chemotherapy with cisplatin, carboplatin and etoposide (CPVP) was conducted in 46 patients with unresectable non-small cell lung cancer. In the previous paper, we showed that CPVP produced a satisfactory response rate without major toxicities. In the present paper, survival time and prognostic factors were analyzed. The median survival time (MST), 1- and 2-year survival of 46 patients (III A4, III B15, IV 27) were 14.1 months, 57.0% and 18.2%, respectively. In prognostic analysis, responders survived significantly longer than non-responders (MST: 15.8 vs 11.0 months, p0.05). Large cell carcinoma and stage IV have proven to be indicators of poor prognosis. Females and patients less than 60 years old tended to do better. With regard to the relationship between the time from initiation of treatment to response and survival time, late responders (response after 3 or 4 courses) survived significantly (p0.05) longer than early responders (response after 1 or 2 courses). The CPVP regimen is not only practical, but also very effective. It deserves further study to reveal its advantages compared to the other platinum compound containing regimens.

35 children between 9 months and 12 years of ages were given 9.1 to 12.2 mg/kg of azithromycin (AZM) once a day for 3 days. In the treatment of pediatric infectious diseases, we studied pharmacokinetics, efficacy and safetiness of AZM. After administration of 10 mg/kg/day of AZM for 3 days, the elimination half-life was calculated to be 3.8 +/- 16.3 hours (n = 6, mean +/- S.D.). The excretion rate of AZM in the urine within 120 hours of administration was 9.0 +/- 2.3% (n = 5). For the evaluation of efficacy of AZM, we treated 33 cases of children with pharyngotonsillitis, bronchitis, mycoplasma bronchitis, pneumonia, mycoplasma pneumonia, atypical pneumonia, and SSTI. The efficacy rate of these cases were 93.9%. 6 strains of bacteria were identified as causative agents. All strains were eradicated upon the treatment. One case of elevated GOT and GPT and two cases of elevated GPT were observed. No clinical adverse reactions were observed. In conclusion, AZM was useful for the treatment of pediatric infectious diseases were examined.