Sand dunes as migrating strings.

We develop a reduced complexity model for three-dimensional sand dunes, based on a simplified description of the longitudinal and lateral sand transport. The spatiotemporal evolution of a dune migrating over a nonerodible bed under unidirectional wind is reduced to the dynamics of its crest line, providing a simple framework for the investigation of three-dimensional dunes, such as barchan and transverse dunes. Within this model, we derive analytical solutions for barchan dunes and investigate the stability of a rectilinear transverse dune against lateral fluctuations. We show, in particular, that the latter is unstable only if the lateral transport on the dune slip face prevails over that on the upwind face. We also predict the wavelength and the characteristic time that control the subsequent evolution of an unstable transverse dune into a wavy ridge and the ultimate fragmentation into barchan dunes.

FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23).

A t(4;11)(q21;q23) has been described in 50-70% of cases of infant acute lymphoblastic leukemia and, less frequently, in cases of pediatric and adult acute lymphoblastic leukemia and acute myeloid leukemia (AML). In t(4;11)(q21;q23) leukemias, the AF4 gene has been cloned as a fusion partner of the MLL gene. A human myeloid leukemia cell line, chronic neutrophilic leukemia (CNL)BC1, was established from a peripheral blood specimen of a patient with CNL in leukemic transformation. As with the original leukemia cells, the established line had a t(4;11)(q21;q23). We showed that the MLL gene on 11q23 was fused to the FLJ10849 gene on 4q21. The protein encoded by FLJ10849 belongs to the septin family, sharing highest homology with human SEPT6, which is one of the fusion partners of MLL in t(X;11)(q13;q23) AML. Our results suggest that FLJ10849 might define a new septin family particularly involved in the pathogenesis of 11q23-associated leukemia. The established cell line, CNLBC1, could provide a useful model for analyzing the pathogenesis of MLL-septin leukemias and chronic neutrophilic leukemia.

T-cell large granular lymphocytic leukemia occurring after autologous peripheral blood stem cell transplantation.

A 61-year-old man with angioimmunoblastic lymphoma in first complete remission underwent autologous peripheral blood stem cell transplantation. At 1 month post transplant, asymptomatic large granular lymphocytosis developed. The surface marker profile of the cells was CD3+CD8+CD56-CD57+. The disease course was chronic and indolent. The patient remains in complete remission from angioimmunoblastic lymphoma more than 6 months post transplant with persistent large granular lymphocytosis (lymphocyte count, 5-15 x 10(9)/l). Although post transplantation T-cell lymphoproliferative disorders have mostly occurred in allogeneic transplantation recipients and presented as aggressive lymphomas/leukemias, we suggest that chronic indolent T-cell large granular lymphocytic leukemia can occur after autologous stem cell transplantation.

Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4+ T lymphocytes.

Although CD4(+) helper T lymphocytes have been demonstrated to play an important role in antitumor immune response, only a few epitopes of tumor-associated antigens recognized by HLA class II-restricted CD4(+) T lymphocytes have been identified. In the present study, we addressed the question of whether leukemia-associated fusion proteins are recognized by CD4(+) T lymphocytes. Immature dendritic cells (DCs) were loaded with necrotic or apoptotic leukemia cells with t(6;9) or t(9;22) and then cocultured with the dek-can fusion peptide-specific or the bcr-abl fusion peptide-specific CD4(+) T lymphocyte clone. The dek-can peptide-specific and bcr-abl peptide-specific CD4(+) T lymphocyte clones produced interferon-gamma (IFN-gamma) when they were cocultured with HLA-DR-matched but not with mismatched DCs which had been loaded with apoptotic as well as necrotic leukemia cells with t(6;9) and t(9;22), respectively. IFN-gamma production by CD4(+)T lymphocyte clones in response to stimulation with DCs loaded with leukemia cells was inhibited by the anti-HLA-DR monoclonal antibody. These data indicate that the acute myelogenous leukemia-associated fusion protein, dek-can, and chronic myelogenous leukemia-associated fusion protein, bcr-abl, are both processed and presented by DCs to the fusion peptide-specific CD4(+) T lymphocytes.

Primary cutaneous aspergillosis caused by Aspergillus ustus following reduced-intensity stem cell transplantation.

A 19-year-old woman with myelodysplastic syndrome underwent reduced-intensity stem cell transplantation [RIST: (cladribine 0.11 mg/kg for 6 days, busulfan 4 mg/kg for 2 days, and rabbit antithymocyte globulin)] from her one HLA-mismatched mother. Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine A (CSA) alone. Severe acute GVHD in the skin, gut, and liver developed concurrently with stable engraftment, and methylprednisolone was administered (1-2 mg/kg per day, then pulse therapy with 1 g/day for 3 days) until day 40 of transplant, when a necrotic lesion of 10 mm in diameter appeared on the right cheek. The initial skin biopsy of the affected area showed a nonspecific inflammatory change. Routine X-ray and computed tomography examinations of the sinuses, chest, and abdomen disclosed no particular abnormalities. Despite intensive antibiotic therapy, the lesion rapidly extended to form an ulcer. A second biopsy specimen obtained from the lesion showed massive septa hyphae, suggesting mold infection. Although we immediately started amphotericin B, she died of multiorgan failure on day 68. Postmortem DNA sequence analysis of the specimen using the polymerase chain reaction identified Aspergillus ustus. Although this is an extremely rare complication after transplantation, this case highlights that we should pay more attention to primary cutaneous aspergillosis in severely immunosuppressed patients.

Suspected delayed immune recovery against cytomegalovirus after reduced-intensity stem cell transplantation using anti-thymocyte globulin.

A reduced-intensity hematopoietic stem cell transplantation (RIST) regimen was developed to induce immunosuppression to facilitate the engraftment of donor cells. However, there have been concerns that the incidence of opportunistic infection may increase after this procedure. To address this problem, we retrospectively analyzed the medical records of 24 RIST recipients who were treated over a recent 16-month period for comparison with 31 recipients of conventional allogeneic transplantation (CST). The RIST regimen consisted of cladribine (0.66 mg/kg), busulfan (8 mg/kg), and rabbit anti-thymocyte globulin (ATG; 5-10 mg/kg). All of the patients received allogeneic peripheral blood stem cells from an HLA-identical or one-locus mismatched related donor. Although the incidence of positive CMV antigenemia was comparable between the two groups (58% vs 68%), RIST patients developed positive antigenemia significantly sooner than did CST patients (P = 0.01) and showed higher initial and maximum antigenemia values (P = 0.026 and P = 0.003, respectively). These findings may suggest that immune recovery against CMV was delayed after our RIST procedure, but this did not directly translate into an increase in clinically significant CMV disease. Early therapeutic intervention with ganciclovir might play a role in preventing the progression of early CMV infection to CMV disease.

Long-term low-dose acyclovir against varicella-zoster virus reactivation after allogeneic hematopoietic stem cell transplantation.

To evaluate the efficacy of long-term administration of acyclovir as prophylaxis against varicella-zoster virus (VZV) reactivation, we analyzed the medical records of 86 consecutive adult patients who obtained engraftment after allogeneic hematopoietic stem cell transplantation from January 1996 to March 2000. We started long-term low-dose (400 mg/day) oral administration of acyclovir in June 1999, and this was continued until the end of immunosuppressive therapy after transplantation. There was no breakthrough reactivation of VZV in patients receiving acyclovir. Five patients who were receiving cyclosporine or prednisolone developed VZV reactivation after discontinuing acyclovir. With this prophylaxis, the cumulative incidence of VZV reactivation at 1 year after transplantation decreased from 33% to 10% (P = 0.025). On multivariate analysis, the use of long-term acyclovir was identified as a significant independent parameter for the development of VZV reactivation. These findings suggest the efficacy of long-term prophylaxis with low-dose acyclovir. Resumption of acyclovir upon restarting immunosuppressive therapy might be important for the further prevention of VZV reactivation. The benefit of long-term low-dose acyclovir should be confirmed prospectively.

Early full donor myeloid chimerism after reduced-intensity stem cell transplantation using a combination of fludarabine and busulfan.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate lineage-specific chimerism reconstitution after reduced-intensity allogeneic stem cell transplantation (RIST) using a combination of fludarabine (30 mg/m2 for 6 days) and busulfan (4 mg/kg for 2 days). DESIGN AND METHODS: We prospectively enrolled 8 consecutive patients with hematologic malignancies who were not candidates for conventional transplantation because of either high age or organ dysfunction. Host-donor chimerism was evaluated using polymerase chain reaction-based amplification of a polymorphic short tandem repeat region. RESULTS: All of our patients achieved engraftment within a median of 11 days after transplantation. On day 30, full donor myeloid cell chimerism (>90%) was achieved in 7 patients whereas full donor T-cell chimerism was achieved in only one patient. Thus, in contrast to other reported results, full donor chimerism was achieved earlier in the myeloid lineage than the T-cell lineage. On day 60, however, T-cell chimerism caught up with myeloid chimerism. Two patients developed grade II-IV acute graft-versus-host disease (GVHD) before the detection of full donor T-cell chimerism. INTERPRETATION AND CONCLUSIONS: Our findings suggest that the kinetics of lineage-specific chimerism depend on the agents used in the conditioning regimen, and may provide insight into the chimerism kinetics and pathogenesis of GVHD. Thus, the strategy for controlling immunosuppression after RIST should be modified according to the type of conditioning regimen applied.

Successful application of nonmyeloablative transplantation for paroxysmal nocturnal hemoglobinuria.

OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder that manifests as hemolytic anemia, venous thrombosis, and deficient hematopoiesis. Although allogeneic hematopoietic stem cell transplantation is considered the only curative therapeutic measure, transplant-related mortality is not negligible. Several studies supported the use of nonmyeloablative stem cell transplantation (NST) for patients of advanced age or with organ dysfunction. Hence, we used NST in a PNH patient who suffered from acute renal failure due to repeated episodes of hemolysis. MATERIALS AND METHODS: We performed NST using a conditioning regimen consisting of cladribine 0.11 mg/kg x 6, busulfan 4 mg/kg x 2, and rabbit anti-thymocyte globulin 2.5 mg/kg x 2. He received peripheral blood stem cells from his human leukocyte antigen-matched brother. Prophylaxis against graft-vs-host disease was performed with cyclosporine A alone. Chimerism of peripheral blood mononuclear cells was evaluated serially using short tandem repeat analysis and flow cytometry. RESULTS: No meaningful regimen-related toxicities were documented. Donor chimerism of 90 to 100% was achieved on day 14 and thereafter. The patient is doing well, without any recurrence of hemolysis 6 months after transplant. Follow-up chimerism studies confirmed stable and functioning donor-type hematopoiesis. CONCLUSIONS: NST may become a safe and curative approach in patients with PNH. Further studies are needed to establish the role of NST for treatment of PNH.

Pre-emptive therapy against cytomegalovirus (CMV) disease guided by CMV antigenemia assay after allogeneic hematopoietic stem cell transplantation: a single-center experience in Japan.

From April 1998 to March 2000, a cytomegalovirus (CMV) antigenemia-guided pre-emptive approach for CMV disease was evaluated in 77 adult patients who received allogeneic hematopoietic stem cell transplantation at the National Cancer Center Hospital. A CMV antigenemia assay was performed at least once a week after engraftment. High-level antigenemia was defined as a positive result with 10 or more positive cells per 50 000 cells and low-level antigenemia was defined as less than 10 positive cells. Among the 74 patients with initial engraftment, 51 developed positive antigenemia. Transplantation from alternative donors and the development of grade II-IV GVHD were independent risk factors for positive antigenemia. Ganciclovir was administered as pre-emptive therapy in 39 patients in a risk-adapted manner. None of the nine low-risk patients with low-level antigenemia as their initial positive result developed high-level antigenemia even though ganciclovir was withheld. Only one patient developed early CMV disease (hepatitis) during the study period. CMV antigenemia resolved in all but two cases, in whom ganciclovir was replaced with foscarnet. In eight patients, however, the neutrophil count decreased to 0.5 x 10(9)/l or less after starting ganciclovir, including three with documented infections and two with subsequent secondary graft failure. The total amount of ganciclovir and possibly the duration of high-dose ganciclovir might affect the incidence of neutropenia. We concluded that antigenemia-guided pre-emptive therapy with a decreased dose of ganciclovir and response-oriented dose adjustment might be appropriate to decrease the toxicity of ganciclovir without increasing the risk of CMV disease.

[Two cases of cardiac aspergillosis with initial onset of arrhythmia during therapy of acute leukemia].

We have reported two women, aged 86 and 84 years, with cardiac aspergillosis with initial onset of arrhythmia during chemotherapy of acute myeloblastic leukemia and primary plasma cell leukemia, respectively. In leukopenia followed by chemotherapy, they suddenly had arrhythmias with high fever. The former had cardiac infarction with complete atrioventricular block and the latter was also cardiac infarction following to atrial fibrillation. In both cases, cardiac aspergillosis was not diagnosed by echocardigraphy but by autopsy. Since cardiac aspergillosis dose not have characteristic features clinically or examinationally, we need to consider arrhythmias revealed in leukopenia as one symptom of cardiac aspergillosis.

Neovascularization with blood-brain barrier breakdown in delayed neuronal death.

Various kinds of acute pathological events in the central nervous system, such as ischemia, hemorrhage, and trauma, often cause brain edema. The edema may advance for days or weeks while inducing extensive damage in neural function, regardless of the extent of the original damage, and often results in death. Delayed edema is thought to be vasogenic; however, the mechanism underlying edema induction remains unknown. We found delayed vascular cell proliferation with a blood-brain barrier breakdown in and around the gerbil CA1 hippocampus, a region known to be involved in delayed apoptotic neuronal death 2-6 days after transient ischemia. Vascular cell proliferation, assessed by (3)H-thymidine incorporation, was most prominent 4-6 days after ischemia, and extravasation of exogenously applied dye or endogenous serum albumin from blood vessels was observed concomitantly. We propose neovascularization in delayed neuronal death as a cause of brain edema advancing days after neurological events.

Differentiation of benign from malignant nodules by accumulation of Tc-99m pertechnetate using TI-201 delayed scans.

Thyroid carcinoma usually is characterized by a nonfunctioning or "cold" nodule depicted on the Tc-99m scan. Twelve patients with functioning "hot" thyroid nodules underwent thyroidectomy (nine hemithyroidectomies, two nodulectomies, and one subtotal thyroidectomy). Histologic examination revealed that five patients (42%) had malignant nodules (papillary carcinoma in two and follicular carcinoma in three). Of the seven patients with benign nodules, five had follicular adenoma and two had adenomatous hyperplasia. TI-201 scanning (early and delayed) was performed at the same time as Tc-99m scanning. Only one of the seven benign nodules showed accumulation on the delayed TI-201 scan, whereas all five malignant nodules showed accumulation. The delayed TI-201 scan is useful for the differentiation of benign from malignant nodules that show accumulation of Tc-99m pertechnetate.

[Analysis of air pollution and prevalence rate of allergic diseases among elementary school children in Kawaguchi and Hatogaya city].

Kawaguchi and Hatogaya City are located on the northern edge of Tokyo. We analysed between air pollution and prevalence rate of allergic diseases among elementary school children in this area. A prevalence rate of allergic diseases in 1996 May and June was as follows; bronchial asthma 13.5%, atopic dermatitis 24.5%, allergic rhinitis and/or conjunctivitis 22.8%, urticaria 12.4%, food allergy 7.8% and drug allergy 2.2%, respectively. Air pollution of this area was analysed to check the levels of nitrogen dioxide (NO2), sulfur dioxide (SO2) and suspended particulate matters (SPM). NO2 pollution was relatively high in urban area, and SPM pollution was especially high around the highways. SO2 pollution was lower than the environmental standard. No relationship was found between the prevalence rate of bronchial asthma, atopic dermatitis, allergic rhinitis and/or conjunctivitis and air pollution, but it was found that these diseases are slightly related to population density (p < 0.1, p < 0.01, p < 0.1, respectively).

[Preoperative evaluation for volume reduction surgery of pulmonary emphysema using MRI: usefulness of HASTE (half-Fourier single-shot turbo SE) sequence during deep respiration].

Volume reduction surgery has recently been an important surgical procedure for patients with severe pulmonary emphysema. We compared the sagittal and coronal images taken by the HASTE sequence with those obtained by turbo FLASH during deep breathing and with CT images obtained under deep inspiration. Clear images were obtained from both sequences, without cardiac or respiratory motion artifacts. The emphysematous areas were demonstrated as low signal intensity areas, as in CT images. The ratio of signal intensity in the expiratory phase to that in the inspiratory phase was lower than that of volunteers in the HASTE sequence. The HASTE sequence provides useful information about respiratory movement as well as about changes in the pulmonary parenchyma when used for preoperative examination.

[A case of tuberculosis in which hemoptysis was caused by bleeding from intercostal arteries].

A 60-year-old man was referred to our hospital because of persistent hemoptysis. Chest roentgenogram and computed tomogram revealed that the right hemithorax was almost completely occupied by solid material with scattered calcifications. Mycobacteria were detected in the sputum culture. Administration of antituberculosis agents began after admission. Four months after admission, massive hemoptysis occurred. Topical treatment via fiberoptic bronchoscopy resulted in no improvement. Surgical resection of the right lung would probably have been difficult because of the almost complete collapse of the right lung and the extensive calcifications within the right hemithorax. Angiographic examination revealed extravasation of contrast medium from the right 7th, 8th, 9th, 10th, and 12th intercostal arteries. After transcatheter embolization of each of these intercostal arteries, hemoptysis stopped. It is unclear how bleeding from intercostal arteries caused massive hemoptysis, but the bleeding may have caused a right hemothorax that drained into an airway.

[Computed tomography findings of malignant pleural mesothelioma].

Computed tomography (CT) findings were assessed in 7 patients with malignant mesothelioma. CT findings were also reviewed in 9 patients with lung cancer and pleuritis carcinomatosa and in 11 patients with tuberculous pleuritis. Five patients with malignant mesothelioma underwent CT scans twice, on admission and from 1 to 7 months after admission. Tuberculous pleuritis could be distinguished from pleuritis carcinomatosa and malignant mesothelioma by the presence or absence of pleural nodularity and chest wall invasion. Although it was difficult to identify specific CT features clearly distinguishing malignant mesothelioma from pleuritis carcinomatosa, characteristic findings of malignant mesothelioma appeared to include the rapid development and progression of pleural rind and a tendency to spread directly into the chest wall. We divided the pleura into the four regions; upper anterior, upper posterior, lower anterior and lower posterior regions. Pleural changes were more frequently seen in the lower pleural regions than in the upper pleural regions, in malignant mesothelioma.

Cavernous hemangioma with arterioportal and arterio-hepatic vein shunts coexisting with hepatocellular carcinoma.

A patient with hepatocellular carcinoma (HCC) and coexisting hepatic cavernous hemangiomas with arterioportal and arterio-hepatic vein shunts is reported. Antegrade and retrograde opacifications of portal vein radicles and filling of a branch of the right hepatic vein verging on cavernous hemangiomas were observed in the late arterial phase of hepatic arteriography in addition to HCC. Unenhanced CT scans performed eight days after the arterial infusion of Lipiodol showed clearly the location of the tumors and the shunting vessels. To the authors' knowledge, this is the first reported case of cavernous hemangioma with arterioportal and arterio-hepatic vein shunts accompanied by hepatocellular carcinoma.

Quantitative evaluation of 99mTc-GSA in the rat liver after ischemia-reperfusion injury.

99mTc-DTPA-galactosyl human serum albumin (Tc-GSA) is a new liver-imaging agent which binds specifically to hepatic binding protein. The purpose of this study was to evaluate the usefulness of Tc-GSA in quantitatively evaluating hepatic ischemia-reperfusion injury in the rat. Regional hepatic ischemia was induced by clamping the left hepatic artery and the left portal vein for 5 to 45 min. A hepatic accumulation index (t90) was obtained on the basis of the dynamic data. A significant difference of this index was observed between all ischemic groups and the control. In conclusion, 99mTc-GSA appears useful for evaluating the hepatic ischemia-reperfusion injury.

[Quantitative evaluation of liver function using 99mTc-GSA in rats with liver injury induced by ischemia-reperfusion].

We evaluated quantitatively the liver injury of rats induced by ischemia-reperfusion, using 99mTc-DTPA-Galactosyl-Human-Serum-Albumin (99mTc-GSA). The vessels of the left lobe were clamped for 5, 10, or 45 minutes followed by 15 minutes reperfusion. Then, 99mTc-GSA was intravenously administered (170 micrograms/kg body weight) to rats. Two compartment analysis was made on measurement curves in the heart and liver to obtain clearance parameters. Significant difference was observed between the ischemic group (clamped for 10 and for 45 minutes) and the control. These results suggest that 99mTc-GSA is useful in the estimation of liver injury produced by ischemia-reperfusion.