Small-amplitude dynamic force microscopy using a quartz cantilever with an optical interferometer.

We propose dynamic force microscopy (DFM) that employs a quartz cantilever in combination with an interferometric deflection sensor. The high stiffness of the quartz cantilever allows DFM to be performed at oscillation amplitudes as small as 1 A. DFM topographic images can be obtained for a Si(111)-(7 x 7) surface even when a blunt tip is used at room temperature. The low-noise interferometer with a deflection noise floor of n = 15 fm Hz(-1/2) exhibits a high force sensitivity in force spectroscopy. By subtracting the huge van der Waals force contribution, we obtain a short-range force curve that is in good agreement with the theoretical curve of the covalent bonding force. Simultaneous measurement of the tunneling current during DFM imaging is also demonstrated.

Caenorhabditis elegans Chk2-like gene is essential for meiosis but dispensable for DNA repair.

A Chk2-like gene was identified in the genome of Caenorhabditis elegans. The putative gene product, termed Ce-chk-2 consists of 450 amino acid residues, and shows good homology with the Chk2/Cds1 gene family. The results of RNA-mediated interference (RNAi) indicated that the F1 generation from dsRNA injected animals grew to adulthood, but approximately 95% of their eggs (F2) died during early embryogenesis. Among the few surviving progeny, males (XO animals) arose at an abnormally high frequency (30%). In addition, 12 univalents were observed in full grown oocytes of the F1, while six bivalents were normally observed in wild-type oocytes. Ce-chk-2 gene expression increased in the adult stage, and their expression level decreased in the glp-4 mutant, which is defective in germ line proliferation. The radiation sensitivity of F1 embryos carrying Ce-chk-2 RNAi was not significantly affected.

Long-term survival and late-onset complications of cancer patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation.

The antitumor effect of high-dose chemotherapy (HDC) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) is considered superior to that of conventional chemotherapy. However, the long-term benefits of this strategy in Japan remain unclear. Therefore, in this study, 109 cancer patients enrolled between 1989 and 1999 were treated with HDC and auto-PBSCT. Patients were evaluated for long-term survival and late-onset complications, including secondary malignancy. The mean number of CD34+ cells harvested per apheresis was larger in the group receiving high-dose cytosine arabinoside or high-dose etoposide plus granulocyte colony-stimulating factor (G-CSF) than in the group receiving conventional chemotherapy plus G-CSF. The 5-year overall survival rates for non-Hodgkin's lymphoma patients in first complete remission (CR) (83.2%), second or subsequent CR (74.1%), or first partial remission (PR) (66.7%) at the time of transplantation were significantly higher than those with no remission (35.7%) at the time of transplantation (first CR, P < .05; second or subsequent CR, P < .05; first PR, P < .05). The 5-year overall survival (OS) rates for breast cancer was 40.8%, and the disease-free survival rate was extremely low (8.8%). The 5-year OS rates for chemotherapy-sensitive and chemotherapy-resistant diseases at the time of transplantation were 32.7% and 35.7%, respectively, a difference that was not considered significant. The 5-year OS for germ cell tumor was 80.0%, and the disease-free survival rate was 77.9%. The rate of therapy-related death was 8.2%. The occurrence rate of secondary malignancy was 0.9%. Late-onset complications were observed in 4 cases (glomerulonephritis, interstitial pneumonitis, ulcerative colitis, and acute myelogenous leukemia). At 3.7%, the occurrence rate was not very high, but most complications of auto-PBSCT were life threatening and interfered with patients' quality of life. A careful follow-up is required for at least 2 years after transplantation, because the mean occurrence time of late-onset complications is 16.7 months posttransplantation.

[Follicular lymphoma associated with t(14;18)(q32;q21) chromosome translocation and bcl-2 gene rearrangement: report of a case].

A 31-year-old Japanese male who complained of low-grade fever, fatigue and generalized lymphadenopathy had shown an increase in peripheral white cell count, and 84% of peripheral blood cell and 76% of nuclear bone marrow cells consisted of small cleaved lymphoblastic abnormal cells with or without barely visible nucleoli. Cytogenic study of cervical lymph node biopsy specimens showed a t(14;18)(q32;q21) chromosome translocation. Histologically the lymph node cells were classified according to the International Working Formulation as follicular small cleaved-cell lymphoma. Molecular analysis of DNA fragments of peripheral lymphocytes revealed both J-H gene and bcl-2 oncogene rearrangements. Immunophenotypes of peripheral lymphocytes, bone marrow cells and lymph node cells expressed a clonally distinct B-cell population bearing surface immunoglobulin-G, kappa-chain, CD-10, CD-19, CD-20, CD-21 and OKIa-1 antigens. We diagnosed this case as follicular lymphoma in the leukemic phase,

[IBL like T cell lymphoma associated with hemolytic anemia and polyploidy chromosomal abnormality--a case report].

A 56-year-old man was admitted to Sapporo Kitano Hospital on May 30, 1987 because of fever, retention of ascites and pleural effusion, generalized lymphnode swelling and hepatosplenomegaly. Laboratory findings showed Coombs' positive hemolytic anemia, leukocytosis and polyclonal hypergammaglobulinemia. Serological test included positive RA factor, anti-DNA 16 U/ml, thyroglobulin Ab 1600 x and microsome Ab 3200 x. A cervical lymphnode specimen exhibited typical histologic picture of IBL like T cell lymphoma. The surface markers of lymphoma cells were CD2(+), CD8(+) and CD4(-). Chromosomal analysis of these cells revealed polyploidy abnormality for all chromosomes except for No. 14's which are disomy. All lymphoma cells have XXY sex chromosome and mar1, mar2, mar3. Gene rearrangement for beta-chain of T cell receptor was proved in these lymphoma cells. He was treated with prednisolone, vincristine, cyclophosphamide, adriamycin etc, but died of respiratory failure 171 days after admission. We reported a rare case of IBL like T cell lymphoma with polyploidy chromosomal abnormality accompanied with hemolytic anemia.

A clinico-pathological study on progress factors in lupus nephritis.

The prognosis of lupus nephritis was investigated in 147 patients who underwent renal biopsy, in an attempt to elucidate the progress factors of this disease clinico-pathologically. Twenty-two patients received a follow-up biopsy and were observed for time-related histopathological changes. At the first examination, only the serum creatinine and mean blood pressure were correlated with prognosis. The anti-DNA antibody and serum complement titer measured at the same time did not correlate with prognosis, and neither showed a significant improvement in the poor prognosis group. Profuse proteinuria tended to last longer in the poor prognosis group. The renal biopsy findings were found to correlate with prognosis. The prognosis was especially poor in patients exhibiting marked mesangial cell proliferation, glomerulosclerosis and interstitial lesions.

[A case of pericarditis carcinomatosa showing good response following local transfer of lymphokine-activated killer (LAK) cells].

A good therapeutic response following local transfer of lymphokine-activated killer (LAK) cells was obtained in a patient with cardiac tamponade due to breast carcinoma. A 41-year-old female was admitted with complaints of dyspnea and tachycardia. She had undergone left mastectomy at the age of 37 years and had received continuous oral administration of tamoxifen. Chest roentgenogram revealed cardiomegaly (CTR = 65%) and cardiac echogram showed marked retention of pericardial effusion. The cytology of the effusion was class V (adenocarcinoma). Cardiac tamponade proved refractory to combination chemotherapy using adriamycin, cyclophosphamide and 5-fluorouracil, and the effect of paracentesis was only temporary. Autologous peripheral blood lymphocytes were obtained through the cubital vein and cultured in vitro with 2 units/ml of human recombinant IL-2, (TGP-3, Takeda Pharm. Co.). After 4 days of cultivation, LAK cells were transferred intrapericardially 3 times. The cumulative infusion dose was 1.2 X 10(8) cells and the amount of combined IL-2 administration was 100 units/each transfer. Twenty-four days after initial infusion of LAK cells, the effusion disappeared. After then, recurrence has not been observed for 287 days. This case is the first trial of LAK therapy against pericarditis carcinomatosa and seems to be a useful way of treating this uncontrollable state without any serious side effects.

[Thrombolytic therapy of pulmonary thromboembolism--result of 18 patients].

In Japan, pulmonary thromboembolism (PTE) is rare and the therapy of this disease, especially the thrombolytic therapy, has not been established yet. We studied the effect of thrombolytic therapy by urokinase (UK) in eighteen patients with PTE. We also compared the results with those in Europe and the United States. Eighteen patients (male 7, female 11) were 27 yo to 77 yo (mean 55 yo). Seven cases were mild and 11 cases were moderate to severe. The initial dosage of UK administration was 2.4 x 10(5) to 7.2 x 10(5) IU with the mean of 4.1 x 10(5) IU, which was approximately the double of those in Europe and the US. The duration of UK therapy was 1 to 9 days with the mean of 4.8 days. It was longer than in Europe and the US (12-24 hours). Total amount of UK in each case ranged 4.8 x 10(5) to 42 x 10(5) IU (mean 19.3 x 10(5) IU) with the daily dosage of 4.0 x 10(5) IU in average. They were almost half of those in Europe and the US. Clinical signs and laboratory findings subsided in 1-7 day by UK administration in 14 cases (87%) with the reduction of defects on perfusion lung scans and all of these cases survived. No severe complications were found in any cases. We conclude that the thrombolytic therapy with UK in Japan might be acceptable from the results of this present study. However, the prospective study of thrombolytic therapy on a larger scale remains to be done in the future.