Fas-mediated apoptosis and p53 mutation in a Hodgkin's disease cell line.
Explore the source record for details and available documents.
Apoptosis↗
Biomedical subjects
I Miyoshi
Publications and source records attributed to I Miyoshi.
PTHrP-mediated hypercalcaemia in a case of CML blast crisis.
We report a 52-year-old man with chronic myelogenous leukaemia (CML) who developed hypercalcaemia in blast crisis. There was a high serum level of parathyroid hormone-related protein (PTHrP). The leukaemia cells secreted PTHrP into culture medium when cultured in vitro and were shown to express PTHrP mRNA by reverse transcription-polymerase chain reaction. Transplantation of the leukaemia cells into nude mice resulted in the production of Ph1 chromosome-positive tumours which caused increased levels of calcium and PTHrP in the blood. These results indicated that the hypercalcaemic event in the patient was induced by PTHrP of CML cell origin.
Blast Crisis↗
Dual infection of rabbits with human T cell lymphotropic virus types I and II.
Attempts were made to generate a rabbit model of dual infection with human T lymphotropic virus (HTLV) types I and II. Four groups (A, B, C, and D) of three rabbits each were used. Group A was inoculated with the RW-1 cell line coinfected with HTLV-I and HTLV-II and group B was transfused from a dually infected rabbit. Polymerase chain reaction (PCR) using primers specific for the pol region of each virus detected both HTLV-I and HTLV-II in all group A and two group B rabbits, but HTLV-II only in the remaining group B rabbit. Groups C and D already infected with HTLV-I and HTLV-II, respectively, were inoculated with an HTLV-II- or HTLV-I-producing cell line. One group C rabbit became PCR-positive for both viruses but the other five resisted superinfection with the respective viruses. During prolonged observation, three of the six dually infected rabbits converted to single (HTLV-I or HTLV-II) infection. The in vivo dual infection was confirmed by in vitro establishment of a lymphoid cell line coinfected with HTLV-I and HTLV-II. It was also possible to establish coinfected lymphoid cell lines from HTLV-I-infected rabbits by coculture with lethally irradiated HTLV-II-producing cells and vice versa. The mechanism of viral elimination in dually infected rabbits, as well as that of protective immunity against superinfection, remains to be elucidated.
Animals↗
Polymerase chain reaction amplification of Asp f I and alkaline protease genes from fungus balls: clinical application in pulmonary aspergillosis.
Asp fI(18 kDa) and alkaline protease (33 kDa) are the 2 major antigens which are derived from Aspergillus (A.) fumigatus and have been implicated as possible virulence factors in the pathogenesis of Aspergillus-induced diseases. We attempted to detect fragments of genes encoding both proteins from fungus balls obtained at surgery or autopsy by polymerase chain reaction (PCR) amplification and then used PCR to test clinical samples. Frozen-stored fungus ball samples from a patient with acute myeloid leukemia complicated by Aspergillus pneumonia and from a patient with pulmonary aspergilloma were studied. We successfully amplified a 315 bp PCR product, the target sequence for Asp f I, and a 747 bp PCR product as a target sequence for alkaline protease (ALP) in both cases. In addition, 13 clinical samples including sputum specimens from patients with pulmonary aspergillosis were also examined. PCR analysis for the Asp f I (ALP) gene in clinical samples showed positive results in 5/10 (6/10) patients with pulmonary aspergilloma and in 3/3 (1/ 3) patients with invasive pulmonary aspergillosis. Culture data on A. fumigatus revealed positive results in 3/9 patients with pulmonary aspergilloma and in 2/3 patients with invasive pulmonary aspergillosis. This method can be used to recognize the involvement of A. fumigatus in various clinical settings where conventional culture results are not readily available.
Adult↗
Expression of Fas and apoptosis of a Hodgkin's disease cell line (HD-70)
Explore the source record for details and available documents.
Apoptosis↗
Human herpesvirus 8 in Kaposi's sarcoma of an HIV-negative Japanese woman with adult T-cell leukemia.
Explore the source record for details and available documents.
Adult↗
Morphological study of pituitary tumorigenesis in transgenic mice induced by hybrid oncogene of the thyrotropin beta-subunit and the simian virus 40 large T-antigen.
We have created a transgenic mouse, TTP-1, generating anterior pituitary tumors by using the simian virus 40 (SV40) large T antigen gene and human thyrotropin beta-subunit gene. To examine characteristics of tumors, histological details were investigated using light and electron microscopies. The main tumor tissues, composed of small chromophobe cells, were located inferior to but clearly separated from the hypothalamus; however, neuron fibers probably derived from the hypothalamus were observed to invade some tumor tissues. Some differentiated endocrine cells occupied the caudal region of the tumor. Immunohistochemically, SV40 large T antigen was expressed in the cell nucleus of the undifferentiated cell area, whereas cells expressing several hormones were mainly distributed in the differentiated cell area. Electron microscopically, the undifferentiated cells were divided into 2 types; electron-dense and -lucent cells, the nuclei of which were composed of obscured nucleoli and many notable invaginations of the nuclear membrane. No intracellular microfilamentous structures were observed. Sometimes it was noted that cytoplasmic processes were connected with gap junctions. In the intercellular spaces, there were neuron fibrous and synapse-like structures. In the differentiated cell area, the cell membranes directly contacting other cells were relatively smooth, and many gap junctions were demonstrated. Secretory granules, which were round and less than 100 nm in diameter, were more electron dense in smaller cells than in larger cells. They were aligned just below the cell membrane. Immuno-electron microscopically, positive reactions for SV40 were observed in the nuclei of the undifferentiated cell area. In the differentiated cell area, most of the secretory granules were labeled by GH. TTP-1 transgenic mice should provide a valuable animal model for studying the pathogenesis of anterior pituitary tumors.
Animals↗
Biphenotypic leukemia with a new translocation, t(2;6)(q31;q23).
A t(2;6)(q31;q23) was found in a patient with acute biphenotypic leukemia. This cytogenetic change has not been reported previously in acute lymphocytic leukemia (ALL) or biphenotypic leukemia, although deletion of 6q has been frequently found in ALL.
Cell Lineage↗
An intensive chemotherapy of adult T-cell leukemia/lymphoma: CHOP followed by etoposide, vindesine, ranimustine, and mitoxantrone with granulocyte colony-stimulating factor support.
SUMMARY: An intensive combination chemotherapy regimen supported by granulocyte colony-stimulating factor (G-CSF) was evaluated in adult T-cell leukemia/lymphoma (ATLL) patients in a multiinstitutional, cooperative study. Vincristine 1 mg/m2 i.v. day 1, Adriamycin 40 mg/m2 i.v. day 1, cyclophosphamide 400 mg/m2 i.v. day 1, prednisolone 40 mg/m2 i.v. days 1 to 3 and 8 to 10, etoposide 35 mg/m2 i.v. days 1 to 8, vindesine 2 mg/m2 i.v. day 8, ranimustine 50 mg/m2 i.v. day 8, mitoxantrone 7 mg/m2 i.v. day 8, and G-CSF 50 mg/m2 s.c. days 9 to 21 were given for 2 to 4 courses every 3 weeks to 83 patients with ATLL. Complete remission (CR) and partial remission (PR) were achieved in 35.8 and 38.3 percent, respectively, of 81 evaluable patients. The median survival of all patients was 8.5 months, with a predicted 3-year survival of 13.5 percent by the Kaplan-Meier method. The median duration of response was 7.6 months (range 0.2-42.7), and 13 patients were alive. Their median survival time was 29.1 months (range 19.2-44.7). In 67.6 percent of courses, white blood cell (WBC) nadirs were < 1.0 x 10(9)/L. Days required for the recovery of WBC from the nadir to > 1.0 x 10(9)/L were <5 days in 71.4 percent of the treatment courses. The G-CSF supported an intensified chemotherapy regimen for ATLL and yielded better response rate and longer survival compared to previous reports in Japan. Because duration of remission is still short, further studies of postremission therapy or other strategies are warranted.
Adult↗
A solid-phase enzyme-linked assay for ceramide glycanase using GM1 and a novel beta-galactosidase inhibitor.
Explore the source record for details and available documents.
Carbohydrate Sequence↗
Acute lymphoblastic leukemia of childhood: identification of two distinct regions of deletion on the short arm of chromosome 12 in the region of TEL and KIP1.
Cytogenetic analysis of acute lymphoblastic leukemia (ALL) of childhood identified nonrandom chromosomal abnormalities of the short arm of chromosome 12. The alterations include deletions that are thought to be indicative of the presence of a tumor suppressor gene that is mutated on the remaining allele. To refine further the chromosomal localization of this gene, we analyzed the loss of heterozygosity (LOH) of chromosome 12 in 100 primary ALL samples using 22 polymorphic markers and identified two distinct smallest common deleted regions on chromosome 12p13. One region is flanked by D12S77 and D12S98 and has a size of 4 cM. Twenty-six percent of informative patients showed LOH in this region. This region may contain the TEL gene. The other region is flanked by D12S269 and D12S308 including the KIP1 gene. Forty-four percent of informative patients showed LOH in this second region. Mutational analysis of KIP1 using polymerase chain reaction-single-strand conformation polymorphism analysis and Southern blot analysis showed no homozygous deletions and point mutations suggesting that the altered gene in this second region is not the KIP1. Clinical data showed that LOH of 12p was demonstrated more frequently in precursor-B ALLs (32 of 80; 40%) than in T-ALLs (1 of 20; 5%) (P = .0027). Furthermore, patients with 12p LOH were younger (P = .013), with a lower DNA index (P = .046), but they had the same survival rates at 3 years. In summary, these data suggest that two different tumor suppressor genes are on chromosome arm 12p, which act separately in the development of childhood precursor-B ALLs. One of the tumor suppressor genes is in the region the KIP1 gene, but our data suggest this gene is not abnormal. The other target is in the region of the TEL gene; and this candidate deserves further study.
Cell Cycle Proteins↗
Frequent loss of heterozygosity in region of the KIP1 locus in non-small cell lung cancer: evidence for a new tumor suppressor gene on the short arm of chromosome 12.
To refine the chromosomal localization of a putative tumor suppressor gene, we analyzed the loss of heterozygosity (LOH) of chromosome 12 in 36 primary non-small cell lung cancer (NSCLC) samples with matched normal DNA using 22 highly informative polymorphic markers. Twelve cases showed LOH at one or more loci on chromosome 12. LOH of chromosome arm 12p was more frequent in large cell carcinoma than squamous cell carcinoma, indicating molecular genetic heterozygosity within the major NSCLC subtypes. We identified the smallest commonly deleted region on chromosome 12p13. This region is flanked by D12S269 and D12S308, including the KIP1 gene. Mutational analysis of KIP1 using PCR-single strand conformation polymorphism and Southern Blot analysis showed no homozygous deletions, rearrangements, or point mutations, suggesting that the altered gene in this region is not the KIP1 gene. These data suggest that a new tumor suppressor gene which is involved in tumorigenesis of NSCLC is in the region of KIP1.
Carcinoma, Non-Small-Cell Lung↗
Adult T-cell leukemia diagnosed after 22 years.
Explore the source record for details and available documents.
Adult↗
HTLV-I-seronegative, genome-positive adult T-cell leukemia: report of a case.
An HTLV-I-seronegative case of adult T-cell leukemia (ATL) carrying the HTLV-I genome is reported. Screening serological tests were negative and Western blot analysis revealed only a faint band for HTLV-I p24. Polymerase chain reaction (PCR) disclosed the presence of HTLV-I gag, pol, env, pX, and LTR sequences in the lymph node and peripheral blood. Southern blot analysis revealed a monoclonal integration of HTLV-I in the lymph node and peripheral blood. The tumor cells expressed viral antigens after short-term culture. The clinical course was consistent with ATL in that the patient exhibited hypercalcemia and abnormal lymphocytosis as well as hepatosplenomegaly and lymphadenopathy. We recommend that PCR analysis for HTLV-I be performed even in seronegative cases when ATL is clinically suspected.
Aged↗
Duplication of del(20)(q11) in a case of MDS.
Explore the source record for details and available documents.
Chromosome Deletion↗
The effects of alpha-phenyl-tert-butyl nitrone (PBN) on copper-induced rat fulminant hepatitis with jaundice.
In the present study we demonstrated the protective effects of the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN) against fulminant hepatitis with jaundice in LEC rats. In LEC rats an excess amount of copper is accumulated in the liver and causes hepatitis with severe jaundice. PBN was subcutaneously administered every 2 d at the concentration of 128 mg/kg, beginning with 13-week-old rats and continuing for 17 weeks. PBN prevented the loss of body weight, reduced death rate, and suppressed the increase in GTP and GOT values reflecting hepatic cell destruction. Ocular inspection also confirmed the suppressive effects of PBN on jaundice. In parallel with these phenomena, the amounts of thiobarbituric acid-reactive substances (TBARS) in livers of PBN-administered rats were found to be lower than those of non-PBN-administered rats. Little histological changes were observed in PBN-administered rats in comparison with non-PBN-administered rats. The protective effect of PBN on the formation of oxidative damage in liver DNA was observed but not so remarkable as that on lipid peroxidation. From these results, it was concluded that PBN had the liver-protective effects against fulminant hepatitis with jaundice. This suggested that free radicals play an important role in abnormally accumulated copper-induced liver injury and that PBN potentially has therapeutic value for the treatment of hepatitis.
8-Hydroxy-2'-Deoxyguanosine↗
Establishment of a clonal cell line producing granulocyte colony-stimulating factor and parathyroid hormone-related protein from a lung cancer patient with leukocytosis and hypercalcemia.
Squamous cell lung carcinoma cells obtained from a patient who presented with leukocytosis and hypercalcemia were transplanted into nude mice and a serially transplantable cell line, OKa-N-1, was established. The nude mice transplanted with OKa-N-1 cells displayed leukocytosis and hypercalcemia. Serum levels of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) were both elevated in these mice. In vitro cultivation of this tumor cell line gave rise to a clonal cell line, OKa-C-1. Nude mice transplanted with the OKa-C-1 cell line also showed leukocytosis and hypercalcemia with high serum G-CSF and PTHrP levels. The culture supernatant of OKa-C-1 contained high levels of G-CSF and PTHrP. Immunohistochemical studies showed the expression of PTHrP in OKa-C-1 cells. Reverse transcription polymerase chain reaction revealed the presence of G-CSF and PTHrP mRNA in this cell line. Dexamethasone treatment inhibited the transcription of G-CSF and PTHrP genes. This new human squamous carcinoma cell line, OKa-C-1, would be useful for studying the mechanism of simultaneous production of G-CSF and PTHrP and their control in cancer patients with leukocytosis and hypercalcemia.
Animals↗
Lung squamous cell carcinoma producing both parathyroid hormone-related peptide and granulocyte colony stimulating factor.
An autopsy case of a 61 year old male with primary squamous cell carcinoma of the lung with associated marked leukocytosis and hypercalcemia is reported. High levels of serum parathyroid hormone-related peptide (PTHrP) and granulocyte colony stimulating factor (GCSF) were detected. The tumor cells distinctly showed positive cytoplasmic immunoreactions with anti-PTHrP and anti-GCSF antibodies. Marked granulocytosis and thin bony trabeculae lacking osteoblasts were observed in the vertebral bone. Calcium deposits were found in the proximal tubules of the kidneys. Infarcts were seen as a result of fibrin thrombosis of the splenic artery. The tumor was successfully transplanted into nude mice in which the high levels of serum PTHrP and GCSF were reproduced. These results indicate that the tumor simultaneously produced both PTHrP and GCSF causing the paraneoplastic syndromes of hypercalcemia and leukocytosis.
Animals↗