Demonstration of the stabilization technique for nonplanar optical resonant cavities utilizing polarization.

Based on our previously developed scheme to stabilize nonplanar optical resonant cavities utilizing polarization caused by a geometric phase in electromagnetic waves traveling along a twisted path, we report an application of the technique for a cavity installed in the Accelerator Test Facility, a 1.3-GeV electron beam accelerator at KEK, in which photons are generated by laser-Compton scattering. We successfully achieved a power enhancement of 1200 with 1.4% fluctuation, which means that the optical path length of the cavity has been controlled with a precision of 14 pm under an accelerator environment. In addition, polarization switching utilizing a geometric phase of the nonplanar cavity was demonstrated.

Morphological classification of dental lesions induced by various antitumor drugs in mice.

To characterize and compare maxillary incisor lesions caused by various antitumor drugs, male BALB/c mice were given a single intravenous injection of an estimated 10% lethal dose (LD10)) of 5-fluorouracil (5-FU), adriamycin (ADR), mitomycin C (MMC), vinblastine sulfate (VBL). taxotere (TXR), irinotecan hydrochloride (CPT-11), DX-8951f, or cisplatin (CDDP). After 3, 5, 10, 15, and 60 days, the animals were sacrificed, and the maxillary incisors were examined microscopically. The dental lesions observed were classified into 4 different types on the basis of their morphological features. The lesion due to 5-FU was characterized by focal defects in the dentin, and this injury was reversible (transient dentin injury). ADR- or MMC-induced lesions were defined by abnormal structure of the apical aspect of the tooth and irregular odontogenesis, lasting for a long period (persistent apical injury). Treatment with VBL or TXR showed irregular enamel formation and abnormal dentinogenesis. Their targets were considered to be both immature and mature odontogenic cells (diffuse dental injury). Exposure to CPT-11, DX-8951f, or CDDP elicited minor reductions in a few precursor cells in the epithelial sheath on day 3, but no prominent dental abnormalities were seen thereafter (nontoxic injury). In conclusion, antitumor drugs can cause a variety of dental lesions that vary temporally and spatially, making histopathological examination of the maxillary incisor an important component of the safety assessment process for novel antitumor drugs.

[Three-dimensional CT angiography of the hepatic artery with multislice CT: differences in image quality according to scanning pitch].

Three-dimensional CT angiography was reconstructed from the hepatic artery using multislice CT, and the effect of pitch during scanning on the quality of obtained images was examined. We randomly divided patients into two groups, with images of one group scanned at helical pitch 3 and images of the other at helical pitch 5.5. CT angiography was reconstructed by a volume-rendering technique. Evaluation was done visually, taking the sharpness of images of branches of the hepatic artery as a measure. Three-dimensional imaging scanned at pitch 3 tended to be better than that scanned at pitch 5.5.

Pathogenetic analysis of three cases with a bleeding disorder characterized by defective platelet aggregation induced by Ca2+ ionophores.

We report three cases of platelet dysfunction characterized by defective Ca2+ ionophore-induced platelet aggregation without impaired production of thromboxane A2 (TXA2). The patients had mild to moderate bleeding tendencies, and their platelet aggregation and secretion induced by ADP, collagen, arachidonic acid, stable TXA2 (STA2) and Ca2+ ionophore A23187 was defective or much reduced. However, ristocetin- or thrombin-induced platelet aggregation was normal. The analysis of second messenger formation showed that inositol 1,4,5-triphosphate formation or Ca2+ mobilization induced by thrombin, STA2 or A23187 was normal. Furthermore, the phosphorylation of 47 kDa protein (pleckstrin) and 20 kDa protein (myosin light chain, MLC) in response to those agonists was normal. These findings suggest that the defective site in the patients' platelets lies in the process distal to or independent of protein kinase C activation, Ca2+ mobilization and MLC phosphorylation.

Tc-99m PMT whole-body scintigraphy for evaluated of therapeutic effect and for monitoring bone metastasis in a patient with hepatocellular carcinoma.

Detection of metastatic lesions by bone scintigraphy is highly sensitive but has a low rate of specificity. Often bone metastases from hepatocellular carcinoma are not detected by bone scintigraphy because of low uptake or a photopenic area in the tumor. In contrast, Tc-99m Sn-N-pyridoxy-5-methyltryptophan (Tc-99m PMT) whole-body scintigraphy reflects tumor viability, and the specificity of detection is so high that tumor structure can be shown well. Tc-99m PMT whole-body scintigraphy was helpful for evaluating the response to therapy and monitoring the course of the patient described here with bone metastasis from hepatocellular carcinoma.

Six different mutations of TGFBI (betaig-h3, keratoepithelin) gene found in Japanese corneal dystrophies.

PURPOSE: To investigate mutations of the human transforming growth factor beta-induced gene (TGFBI), transforming growth factor-beta-induced gene product (betaig-h3, keratoepithelin), in Japanese patients with Avellino corneal dystrophy (ACD), lattice corneal dystrophy (LCD), granular corneal dystrophy (GCD), and Reis-Bücklers corneal dystrophy (RBCD). METHODS: Genomic DNA was extracted from the peripheral blood of 75 patients and 7 unaffected relatives from 60 families with ACD, 34 patients and 8 unaffected relatives from 21 families with LCD, 4 patients and 4 unaffected relatives from 4 families with GCD, and 4 patients and an unaffected relative from 3 families with RBCD. Fifty normal volunteers served as controls. Exons 4, 11, and 12 of the TGFBI gene were amplified by polymerase chain reaction and were directly sequenced. RESULTS: Six different heterozygous missense mutations were detected in codons R124, L518, L527, and R555 of the TGFBI gene in the 117 patients from 88 families. A R124H mutation was detected in the patients with ACD. A R124C mutation was detected in the patients with LCD type 1 (LCD1), L518P was in atypical LCDI, and L527R in LCD with opacities deep in stroma. A R555W mutation was detected in the patients with GCD. A R555Q mutation was detected in the patients with RBCD. CONCLUSIONS: We conclude that codons R124 and R555 of the TGFBI gene are also hot spots in Japanese patients with ACD, LCD, GCD, and RBCD. Many Japanese patients with CD had ACD with R124H mutation. GCD with R555W mutation was rare.

Stereoscopic display of a three-dimensional image of the larynx using high-speed helical scanning.

To evaluate the usefulness of stereoscopic images of larynges using helical CT in stereo mode, a retrospective review of the characteristics of stereoscopic viewing of larynges was made. The subjects were 3 patients with laryngeal cancer, 1 patient with laryngeal leiomyosarcoma and 1 patient with an advanced tongue carcinoma whose formalin-fixed larynx was extirpated. The larynges were scanned by high-speed helical CT using 1- to 2-mm slices. The reproduction of stereographic images was performed by the manipulation and rotation of three-dimensional structures around the y-axis on the computer display. The three-dimensional images of the complex structures, such as the arytenoid cartilage, aryepiglottic fold and pyriform sinus, were better observed by binocular images (stereograms) than by monocular images. Stereoscopic views of the larynx are useful in producing three-dimensional images of the unseen inner surface of the human body.

5q- syndrome presenting chronic myeloproliferative disorders-like manifestation: a case report.

A 28-year-old Japanese woman with suspected essential thrombocythemia (ET) had marked thrombocytosis, mild leukocytosis with normal neutrophil alkaline phosphatase activity, and no anemia. She was monitored without being given any medication. Eleven years later, complete blood counts showed no remarkable changes but some non-lobulated mononuclear megakaryocytes were found in the bone marrow. Cytogenetic analysis revealed deletion of the long arm of chromosome 5 (5q-). Subsequently, hemoglobin and platelet counts decreased gradually, splenomegaly appeared and progressed, after which myelofibrosis developed. Acute leukemia developed 16 years after the first documentation of thrombocytosis. 5q- syndrome is known to be a myelodysplastic syndrome (MDS) with unique clinical features and cases with this syndrome presenting with thrombocytosis of more than 1,000 x 10(9)/L but without anemia are rare. Furthermore, it is noteworthy that in this patient transition to acute leukemia occurred following development of myelofibrosis and marked splenomegaly, which are generally observed in blastic crises resulting from chronic myeloproliferative disorders (CMPD). The patient showed features indicative of CMPD rather than of MDS in spite of presenting with 5q- chromosomal abnormality. This case supports the concept of "mixed myelodysplastic and myeloproliferative syndromes" and suggests the possibility of the appearance of CMPD-like manifestations in 5q- syndrome.

Expression of coxsackievirus and adenovirus receptor in hearts of rats with experimental autoimmune myocarditis.

The expression of coxsackievirus and adenovirus receptor (CAR) was dominant in the brains and hearts of mice until the newborn phase. There is no detailed information concerning the relation between the expression of CAR and development of hearts. It is also uncertain whether CAR is able to be induced in adult hearts after cardiac injury. We demonstrated that CAR was abundant in the hearts of newborn rats but was barely detectable in the hearts of adult rats. The expression of CAR in rat hearts with experimental autoimmune myocarditis, which was induced by immunization of purified cardiac myosin, was serially investigated. Active myocarditis was observed from day 15 after immunization. By immunohistochemistry, cardiomyocytes were strongly stained for CAR antibody from days 24 to 42. CAR mRNA was also detected from days 18 to 30 by using reverse transcription-polymerase chain reaction. In the next experiment, the induction of CAR on isolated cardiomyocytes was investigated. CAR was barely detectable in cultured cardiomyocytes by Western blot analysis after isolation. This molecule gradually appeared along with the creation of clusters and beating of cardiomyocytes. Furthermore, the induction of CAR in cultured cardiomyocytes increased after supplement with conditioned medium of rat splenocytes activated by concanavalin A. In conclusion, rat CAR is expressed strongly in the hearts of newborn rats and is suppressed in those of adult rats. The expression of CAR is enhanced during the active phase of experimental autoimmune myocarditis and is induced by inflammatory mediators. CAR may play a role in cell-to-cell contact and adhesion of cardiomyocytes.

Inhibition of ATRA-induced myeloid differentiation in acute promyelocytic leukemia by a new protein tyrosine phosphatase inhibitor, 3,4-dephostatin.

We previously reported that the expression and the activity of SHP-1, a non-transmembrane protein tyrosine phosphatase (PTPase) increased during myeloid differentiation of an acute promyelocytic leukemia cell line (HT93) induced by all-trans retinoic acid (ATRA). To examine whether inhibition of SHP-1 activity attenuates myeloid differentiation, we used a new PTPase inhibitor, 3,4-dephostatin, and studied its effect on myeloid differentiation. Suppressive effects on immunoprecipitated SHP-1 phosphatase activity and myeloid cell differentiation were detected. These results suggest that SHP-1 is a substrate for 3,4-dephostatin, and that SHP-1 PTPase activity is closely related to myeloid differentiation.

Esophageal varices before and after endoscopic variceal ligation: evaluation using helical CT.

The purpose of this study was to demonstrate the utility of helical CT in assessing the therapeutic effects of endoscopic variceal ligation (EVL). Twenty-four patients with esophageal varices were examined. Helical scanning was initiated 60 s after intravenous injection (Iopamidol 300 mgI/ml, total 120 ml, 3 ml/s) was started. Esophageal varices were clearly depicted as high-density areas. Multiplanar reformation and 3D images demonstrated collateral circulation three-dimensionally. After EVL, mucosal high-density areas had diminished markedly, but collateral veins around the esophagus, and gastro- and/or spleno-renal shunts, were unchanged in all patients. Of 21 patients with collateral circulation, esophageal varices recurred endoscopically in 6 patients within 12 months. In 3 patients without collateral circulation, esophageal varices did not recur within 12 months. From these findings, we conclude that helical CT is a useful method for assessing the therapeutic effects of EVL.

Decreased expression of the mRNA for somatostatin in the periventricular nucleus of depression-model rats.

Expression of the mRNA for somatostatin (SRIF) in the periventricular nucleus (PeN), the level of SRIF in the stalk-median eminence (SME) and the concentration of growth hormone (GH) in the plasma were examined in depression-model rats in an attempt to confirm the hypothesis that SRIF neurons in the hypothalamus are hypofunctional in this model. We exposed male Wistar rats to intermittent walking stress for two weeks and then we measured their spontaneous running activity for 12 days. We divided the rats into a depression-model group and a partial-recovery group according to the spontaneous running activity of each rat after the termination of exposure to stress. Expression of SRIF mRNA in the PeN of the hypothalamus was monitored by in situ hybridization and relative levels were determined with an image analysis system. The relative level of expression of SRIF mRNA in the PeN was lower in rats in the depression-model group than in the control group and the partial-recovery group. The level of SRIF in the SME was lower and the plasma concentration of GH was higher in the depression-model group than in the other groups. Our findings suggest that reduced expression of mRNA for SRIF in the PeN might be associated with the pathophysiology of rats with this particular model of depression.

Three-dimensional computed tomographic angiography of pulmonary vessels.

OBJECTIVE: To assess the image quality of multiple threshold display (MTD) as a new technique for generating three-dimensional (3D) pulmonary computed tomographic (CT) angiographic images. METHODS: We used MTD, a type of shaded surface display (SSD) offering the selection of multiple thresholds and transparencies, to reconstruct 3D-CT angiograms from enhanced helical CT data sets in 33 patients with lung disease. In MTD, eight thresholds of CT values are selected, and transparency is assigned to each. The selected voxels, ranging from -600 to 1,000 Hounsfield Units, were divided into eight classes, and transparency ranging from 0 to 100% was assigned to each. The CT scanner employed was a Toshiba Xvigor. MTD and SSD images were generated by using an Xtension with a Sun SPARC station 20, and they were compared by two radiologists. RESULTS: The image quality of MTD images was superior to that of SSD images (p < 0.01), because the MTD images demonstrated clearly both the major and small vessels. CONCLUSION: MTD is a useful technique for 3D pulmonary CT angiography.

Involvement of SHP-1, a phosphotyrosine phosphatase, during myeloid cell differentiation in acute promyelocytic leukemia cell lines.

We investigated the modulation of the expression and phosphatase activity of SHP-1 during granulocytic differentiation of human myeloid leukemia cell line, HL60 and t(15;17) positive APL cell line, HT93, in response to all-trans retinoic acid (ATRA) or dimethylsulfoxide (DMSO). ATRA induced differentiation in both cell lines which was associated with marked growth inhibition and S-phase reduction. On the other hand, DMSO induced it only in HL60 without obvious growth inhibition and S-phase reduction. The expression and phosphatase activity of SHP-1 were upregulated only when the 2 cell lines were differentiated to granulocytes. Furthermore, the changes were not dependent on the inducers or the growth inhibition. These findings suggest that SHP-1 is involved in common myeloid differentiation, and that upregulation of SHP-1 is not always related to myeloid cell growth.

Relationship between intracellular calcium-dependent process and protein-tyrosine phosphorylation in human platelets: studies of platelets from a patient with defective A23187-induced platelet aggregation.

We had postulated that in a patient with defective calcium ionophore (A23187)-induced platelet aggregation, whose platelets showed normal intracellular Ca2+ mobilization in either the presence or absence of extracellular Ca2+ in response to A23187. A defect was present in an intracellular calcium-dependent process. We have now investigated whether the agonist-induced protein-tyrosine phosphorylation (PTP) was altered. Protein-tyrosine phosphorylation (PTP)-induced by A23187 in the patient's platelets was greatly diminished but that induced by thrombin was almost normal. These results suggest that an intracellular calcium-dependent process plays a fundamental role in A23187-induced PTP, whereas it does not in thrombin-induced PTP.

Three-dimensional imaging of laryngeal cancers using high-speed helical CT scanning.

To evaluate the clinical usefulness and limitations of three-dimensional (3-D) imaging of laryngeal cancers by high-speed helical (spiral) CT scanning, 3-D images were reconstructed for one dissected human larynx and 10 patients with laryngeal cancer. The larynges were scanned in 1- to 2-mm slices, and were reconstructed using a slice thickness of 0.5-1.0 mm. The macroscopic (or endoscopic) findings and the 3-D CT images of the larynx were compared. The selected threshold CT values were -600 HU (Hounsfield units) to -100 HU for the mucous membranes, and 250 HU for bone. Under these conditions, almost all of the structures remained distinct. The 3-D images of the larynx obtained by helical CT were very helpful in understanding laryngeal anatomy, especially in the subglottic area, which cannot be seen clearly by endoscopy or conventional axial CT. Clinically, this system would have advantages in the detection of subglottic cancers, or the invasion of glottic or supraglottic cancers into the subglottic area.

Hematopoietic cytokine-dependent differentiation to eosinophils and neutrophils in a newly established acute promyelocytic leukemia cell line with t(15;17).

We recently established an acute promyelocytic leukemia (APL) cell line (HT93) that has the capacity to differentiate into neutrophils and eosinophils in response to all-trans retinoic acid (ATRA) and human hematopoietic cytokines. The cells had a myeloblastic morphology, were positive for surface CD33, CD34, and CD56, and showed the following karyotypes: 46, XY, t(1;12)(q25;p13), 2q+, t(4;6)(q12;q13), and t(15;17)(q22;q11). When the cells were cultured with ATRA, they showed nuclear segmentation and developed secondary granules consisting in part of neutrophils and eosinophils. In the presence of ATRA and granulocyte colony-stimulating factor (G-CSF), the cells showed polymorphonuclear neutrophil differentiation accompanied by expression of surface CD11b, CD15, CD10, positive activity for neutrophil alkaline phosphatase (NAP), and NAP mRNA expression. In cultures with ATRA and granulocyte-macrophage colony-stimulating factor (GM-CSF), IL (interleukin)-3, or IL-5, HT93 showed remarkable eosinophil maturation at day 8 as determined by luxol fast blue staining, in addition to expression of eosinophil peroxidase and major basic protein. These results indicate that HT93 is an APL cell line with the ability to differentiate into neutrophils and eosinophils, and that these lineages are dependent on the CSF added. HT 93 should prove to be a useful model in analyzing the effects of hematopoietic cytokines on proliferation, differentiation, and maturation of hematopoietic progenitors.

Characterization and sensitivity to interleukin 2 and interferon alpha of leukemic cells from a patient with large granular lymphocytic leukemia associated with chronic active Epstein-Barr virus infection.

A patient presented with chronic large granular lymphocyte leukemia associated with chronic active Epstein-Barr virus infection (CAEBV). Cell cycle analysis revealed a minimal growth compatible with chronic lymphocytic leukemia After 5 months of treatment, the patient died from acute transformation of the leukemia. Cell harvested during chronic phase were analyzed for sensitivity to interleukin 2 (IL-2) and interferon alpha (IFN alpha) in vitro by means of surface phenotyping and cell cycle assay. IL-2 induced remarkable growth of the cells, whereas IFN alpha did not confer a growth advantage. Since IFN alpha was expected to have no growth induction effect on the leukemia cells, it was administered to the patient to treat the CAEBV.

Prediction of growth sensitivity of acute promyelocytic leukemia cells to granulocyte colony-stimulating factor using 7AAD/PY during administration of all-trans retinoic acid.

We discussed utility of cell cycle and phenotypic analysis of acute promyelocytic leukemia (APL) cells using 7AAD/PY for the prediction of efficacy and risks of all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF) administration to patients with APL. Serial changes in phenotype and cell kinetics of APL cells from two patients were analyzed during ATRA administration. CD15 and CD11b were expressed on the APL cells in vivo as neutrophil maturation markers, while growth activity of the cells was decreased during ATRA administration. Using 7AAD/PY, changes in phenotype and cell kinetics were clearly detected after 2 days of cultivation with ATRA and/or G-CSF. In one patient, APL cells harvested from marrow during the first 3 weeks of ATRA administration showed distinct growth sensitivity to G-CSF ex vivo, and the cells harvested after a 4-week exposure to ATRA appeared to have lost this sensitivity. In this patient, G-CSF could be safely administered after 4 weeks of ATRA therapy. 7AAD/PY analysis is useful for predicting growth sensitivity of APL cells to G-CSF during ATRA administration.

Acquired immune thrombocytopenia caused by IgG antiglycoprotein Ib antibody in a patient with Hodgkin's disease.

We studied a patient with thrombocytopenia associated with Hodgkin's disease (HD). The megakaryocyte number in the bone marrow and the level of platelet-associated IgG were both increased in the patient. Intravenous gamma-globulin therapy and chemotherapy for HD dramatically normalized the platelet count, suggesting that antibody produced by lymphoma cells is likely to account for the thrombocytopenia. Antigen-captured ELISA and Western blotting showed that the patient's serum had an IgG autoantibody against platelet membrane glycoprotein Ib. The patient's plasma had no inhibitory effect on normal platelet aggregation induced by ristocetin. These findings suggest that the autoantibody found in the patient had a pathogenetic role in the thrombocytopenia, but not in platelet dysfunction.