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Biomedical subjects

K Dan

Publications and source records attributed to K Dan.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Corneal abrasion after general anesthesia despite application of eye patches].

A 37-year-old man with exophthalmos underwent resection of the left apical peridontal cyst under general anesthesia. Eye patches (Opticlude) without adherence to epibulbar area were used during anesthesia and surgery. At the end of the surgery, his left eyelid was noted to be incompletely closed. His left bulbar conjunctiva showed marked conjestion with severe pain. Staining with fluorescein dye demonstrated corneal abrasion in the lower third of the left eye. The corneal abrasion healed in two days after topical treatment.

Adult↗
PubMed1998

CD4(+) cytotoxic T-cell clones specific for bcr-abl b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner.

Although it is well known that CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the suppression of cancer cell growth, the significance of CD4(+) CTLs in resistance to cancer is obscure. In an attempt to elucidate the role of CD4(+) CTLs in immunosurveillance of chronic myelogenous leukemia (CML), we examined the immunologic functions of bcr-abl b3a2 fusion peptide-specific CD4(+) CTL clones. Seven CD4(+) T-cell clones that responded to stimulation with b3a2 peptide, but not with b2a2 peptide or physiological counterparts bcr b3b4 and abl 1A-a2 peptides, were established from two healthy individuals. Restriction elements of these clones were HLA-DRB1*0901. These CD4(+) T-cell clones exhibited b3a2 peptide-specific and HLA-DRB1*0901-restricted cytotoxicity and produced interleukin-3 (IL-3), IL-4, IL-10, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor in response to bcr-abl peptide stimulation, indicating they were Th0 clones. The numbers of HLA-DRB1*0901-positive b3a2, but not those of b2a2-positive or HLA-DRB1*0901-negative CML cell colonies increased when CML cells were cultured with b3a2-specific CD4(+) CTL clones. These data suggest that bcr-abl-specific CD4(+) CTLs recognize CML cells in an antigen-specific and HLA-DR-restricted manner, and that they do not inhibit, but in fact augment, CML cell growth.

Amino Acid Sequence↗
PubMed1998

Relation between microsatellite instability and N-ras mutation and duration of disease free survival in patients with acute leukemia.

BACKGROUND: Microsatellite instability (MIN) appears to be a novel molecular mechanism in carcinogenesis and is believed to reflect multiple replication errors. The authors analyzed MIN in de novo acute leukemia and its association with expression of the human MSH3 (hMSH3) gene and point mutations of the N-ras gene. The relation between MIN and disease free survival also was examined. METHODS: The authors studied 43 cases of de novo acute leukemia for MIN at 5 loci. They also examined expression of the hMSH3 gene using the reverse transcriptase-polymerase chain reaction method. DNA taken from 36 cases at diagnosis was examined for N-ras mutations. The Kaplan-Meier method was used to estimate patients' disease free survival. RESULTS: MIN at 1 locus was found in 7 of the 43 cases (16%) (MIN positive [MIN+] group). There was no correlation between MIN+ and decreased hMSH3 gene expression. Four of the 7 MIN+ cases (57%) had a mutation of the N-ras gene compared with only 1 of the 29 MIN- cases (3%). A correlation between N-ras mutations and MIN was detected (P < 0.003). The MIN+ patients had a shorter disease free survival than the MIN- patients (P < 0.03). CONCLUSIONS: MIN may be associated with N-ras mutation in some cases of de novo acute leukemia and influence the duration of disease free survival.

Acute Disease↗
PubMed1998

Extramedullary presentation of chronic myelogenous leukemia with p190 BCR/ABL transcripts.

We present here a rare case of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia having p190 BCR/ABL with a malignant clinical picture of extramedullary blast crisis at onset, followed by rapid evolution to bone-marrow blast crisis. The patient was a 44-year-old woman presenting with leukocytosis and multiple lymph-node swelling in the neck. Lymph-node biopsy revealed a myeloperoxidase-positive blastoma with cell-surface markers of myeloid and T-lymphoid lineages. Fluorescence in situ hybridization and the reverse transcription polymerase chain reaction detected a minor BCR breakpoint but failed to detect a major BCR breakpoint. By single-strand conformation polymorphism and direct sequencing, no alteration in the TP53 gene was found, and no additional chromosomal abnormalities other than Ph were identified. The present case suggests that p190 BCR/ABL is associated with the aggressive course of the disease.

Adult↗
PubMed1998

Establishment of a cell line with variant BCR/ABL breakpoint expressing P180BCR/ABL from late-appearing Philadelphia-positive acute biphenotypic leukemia.

In acute leukemia (AL) with a late-appearing Philadelphia (la-Ph) translocation, it is unclear whether these translocations arise from the same molecular event as classical Ph translocations. In order to elucidate the molecular events of la-Ph and subsequent translocations of la-Ph leukemia, we performed molecular analysis on the complex rearrangements, in a cell line, MY, which was established from bone marrow mononuclear cells of a patient with a la-Ph acute biphenotypic leukemia. This la-Ph, expressing an acute lymphoblastic leukemia (ALL)-type BCR/ABL transcript, produces a novel P180BCR/ABL fusion protein reflecting deletion of 174 bases (58 amino acids) encoded by the a2 exon of the ABL gene. An immune complex kinase assay showed that this protein had autophosphorylation activity. Fluorescence in situ hybridization (FISH) in conjunction with G-banding analysis revealed that the initial der(9)t(9;22)(q34;q11) progressed to a der(9)(9pter-->9q34::22q11-->22q13::5q11.2 -->5q15:: 10q23-->10qter) by, first, a three-way translocation among the der(9)t(9;22)(q34;q11), chromosome 5, and the normal chromosome 22, and then a subsequent translocation with chromosome 10. Moreover, both the end-stage leukemic cells of the patient and the MY cell line had another translocation, t(X;12)(p11.2;p13). The 12p breakpoint was located near the ETV6 gene by analysis of pulsed-field gel electrophoresis, but transcription of ETV6 was unaffected. Tumorigenicity analysis indicated that an additional translocation, t(2;3)(p16;q29), may have caused a more malignant clone, because only MY cells with the t(2;3)(p16;q29) were capable of growing subcutaneously in nude mice within 40 days. The molecular events of leukemogenesis and leukemic progression in the present la-Ph AL occurred by accumulation of unique translocations. This cell line, MY, expressing a novel variant P180BCR/ABL protein with a deletion of the a2 exon of the ABL gene, may be useful for elucidating the pathophysiology of this fusion protein and for studying ETV6-related leukemogenesis and t(2;3), as well as the molecular mechanisms of the complex translocations.

Amino Acid Sequence↗
PubMed1998

Repeated cycles of G-CSF-combined postremission chemotherapy for acute myeloid leukemia in a first complete remission: a pilot study.

The cure rate of acute myeloid leukemia might increase if G-CSF were given concurrently with repeated postremission chemotherapy. However, this therapy might cause severe complications, including depletion of normal hematopoietic progenitors as a long-term toxicity. Thus, we conducted a pilot study of this strategy. Twenty-six acute myeloid leukemia patients in a first complete remission (CR) were treated with two courses of consolidation chemotherapy (10-day BHAC-DMP, consisting of behenoyl cytosine arabinoside, daunorubicin, 6-mercaptopurine and prednisolone) and repeated maintenance-intensification therapy including eight cycles of six-day BHAC-DMP. G-CSF (filgrastim) was administered concurrently with these BHAC-DMP therapies. Toxicity during the therapeutic period was not significant in the study group compared with the historical control, treated with the same regimen without G-CSF. Neutrophil recovery after the consolidation therapy was more rapid in the study group than in the historical control (p = 0.066 and 0.024 for the first and second consolidation courses, respectively). Long-term toxicity, such as cytopenia, has not been seen in eight patients who have remained in CR for a long period (range: 39-58 months). At a median follow-up of 39 months, the predicted rate of 42-month CR duration for these 26 patients was 50% (95% confidence limits: 30% to 71%). We conclude that G-CSF-combined repeated BHAC-DMP postremission therapy is feasible. Full elucidation of the clinical benefit of this strategy will require further study.

Acute Disease↗
PubMed1998

Genotype configuration in a case of primary gastric lymphoma with T-cell phenotype.

T-cell malignant lymphoma of the gastrointestinal tract is rare. The genotype of gastric T-cell lymphoma remains unclear. The aim of this study was to elucidate the pathogenesis of a case of primary gastric T-cell lymphoma by using cytogenetics and molecular biology. Gastric biopsy specimens and lymphoma cells in the ascites were examined by immunocytology, cytogenetic analysis, and Southern blot analysis. The histological diagnosis of the gastric lymphoma was diffuse large cell type. T-cell markers were positive in immunocytochemistry of the gastric lymphoma cells and in FACS analysis of lymphoma cells in the ascites. All lymphoma cells in the ascites had complex abnormal karyotypes containing t(8;14)(q24;q32). Southern blot analysis revealed rearrangement of the IgH and C-MYC genes of the lymphoma cells in both the stomach and the ascites, but no comigration of the C-MYC with the JH locus could be detected. The TCR-beta and -gamma genes were in their germ-line configurations. In this patient, although the phenotype was T-cell lymphoma, the karyotype t(8;14)(q24;q32) and genotype had the characteristics of B-cell lymphoma. The unique B-cell genotype configuration and the C-MYC activation suggested that the cellular origin of this rare case of malignant lymphoma with a T-cell phenotype was quite immature lymphocytes.

Adult↗
PubMed1998

Quantitation of herpes simplex viral DNA in Vero cells for evaluation of an antiviral agent using the polymerase chain reaction.

A method for quantitation of the DNA of Herpes simplex virus type 2 (HSV-2)-infected Vero cells by the polymerase chain reaction (PCR) was developed. This method allowed recognition of several molecules of viral DNA among the total DNA extracted from cells. The method could be applied to a very large range (10(-0)-10(-7)) of initial amounts of template. Products of PCR were collected after each cycle for kinetic analysis. Products were subjected to electrophoresis and amplified bands were stained with ethidium bromide. The intensity of fluorescence of each band was measured with a charge-coupled device (CCD) image analyzer. The time course of increases in the relative yield of viral DNA was determined. Two-fold amplification of viral DNA occurred each 6-h cycle from 7 h after infection. Using this method, the yields of viral DNA after treatment with the drug acyclovir (ACV) at 0.1 and 2 microg/ml were about 1/10 and 1/80 of those from nontreated infected cells, respectively. These results indicate that this method makes clear the inhibitory effect of ACV on the synthesis of viral DNA.

Acyclovir↗
PubMed1998

Alterations in the colorectal carcinoma gene and protein in a novel human myeloid leukemia cell line with trisomy 18 established from overt leukemia after myelodysplastic syndrome.

A new human myeloid leukemia cell line (OIH-1), with alterations in chromosome 18 and the deleted in the colorectal carcinoma (DCC) gene and its product, was established from the peripheral blood (PB) of a patient with acute myeloblastic leukemia (AML) after myelodysplastic syndrome (MDS). Serial cytogenetics showed the presence of two clones, one with i(18)(q11) and another with trisomy 18. Southern blot analysis of OIH-1 cells with i(18)(q11) showed an extremely reduced intensity of 20- and 14-kb EcoRI fragments, suggesting the allelic loss of the DCC gene. Immunoprecipitation (IP) analysis by the murine monoclonal antibody (MoAb) AF5, specific for the DCC extracellular domain, failed to detect normal 180-kDa DCC protein, however extra 85-kDa protein was detected. However, Southern blot analysis of the latter clone of OIH-1 with trisomy 18 showed normal structure of the DCC gene. IP analysis with AF5 or G92-13 (specific for the extracellular domain) did not detect the DCC protein, but a 150-kDa protein other than the DCC-specific 180-kDa protein was detected with G97-449, specific for the cytoplasmic domain of the DCC protein. RT-PCR analysis showed the expression of the DCC mRNA in OIH-1 cells carrying each type of chromosome 18 abnormalities. These alterations in the DCC gene and protein may contribute to progression of malignancy for OIH-1 cells. The OIH-1 cell line may be useful for studying the role of the DCC gene in leukemogenesis of MDS or AML.

Aged↗
PubMed1998

Pulmonary toxicity after granulocyte colony-stimulating factor-combined chemotherapy for non-Hodgkin's lymphoma.

Sporadic cases have developed pulmonary toxicity after receiving chemotherapy and granulocyte colony-stimulating factor (G-CSF). However, because such cases received chemotherapy that alone frequently causes pulmonary toxicity, the role of G-CSF in this toxicity has been unclear. CHOP therapy (cyclophosphamide, doxorubicin, vincristine and prednisolone) only slightly induces pulmonary toxicity. However, we observed a considerable incidence of this toxicity in non-Hodgkin's lymphoma subjects receiving CHOP therapy and G-CSF (6 out of 52 subjects, 11.5%). In this cohort, among various characteristics, including the dose and interval of CHOP therapy, only the mean peak leucocyte count (MPLC) with each therapy cycle was associated with development of this toxicity (MPLC > or = 23.0 x 10(9) l(-1), 6 out of 29 cases; MPLC < 23.0 x 10(9) l(-1), 0 out of 23 cases; P = 0.020). These findings suggest that the effect of G-CSF is the main determinant of the pulmonary toxicity in these cases. Because the toxicity was associated with a large MPLC and did not recur in cases readministered G-CSF, an idiosyncratic reaction to G-CSF is unlikely to be the pathogenesis of this toxicity. Thus, lowering the G-CSF dose seems to be useful in the prevention of this toxicity. In all six cases, the time course of manifestation of the toxicity was the same, and early application of high-dose corticosteroid led to cure. This knowledge will be helpful in the care of similar cases.

Adult↗
PubMed1998

IL-6 and SCF exert different effects on megakaryocyte maturation.

Megakaryocytic maturation has two aspects, nuclear maturation and cytoplasmic maturation, both of which are affected by several thrombopoietic cytokines. We cultured murine bone marrow cells separated by BSA velocity sedimentation which contained more immature megakaryocytes with lower ploidy in order to study the effects of rhIL-6 and rmSCF on the two aspects of megakaryocyte maturation. During culture with rhIL-6 or rmSCF for 4 d, the megakaryocytes underwent endomitosis, resulting in DNA polyploidization. These two cytokines had different effects on cytoplasmic maturation. Flow cytometry showed that the megakaryocytes cultured with rhIL-6 became larger and had a more complex intracellular structure than those cultured with rmSCF. Morphological studies showed that the megakaryocytes cultured with rhIL-6 were larger and more granular, whereas those cultured with rmSCF were smaller and more basophilic. rhIL-6 promoted cytoplasmic process formation by the megakaryocytes, but rmSCF did not. Analysis of transcripts of PF-4 and GPIIb by RT-PCR suggested that rmSCF kept more megakaryocytes at the protein synthesis stage than did rhIL-6. Based on our findings, these cytokines exert different effects on megakaryocytic cytoplasmic maturational events.

Animals↗
PubMed1998

Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes.

Data on endogenous thrombopoietin (TPO) levels and their regulation in myelodysplastic syndromes (MDS) are sparse. We examined the plasma TPO level of 85 MDS patients by a sensitive enzyme immunoassay and the platelet expression of TPO receptor (TPO-R) protein, which metabolizes endogenous TPO, in 19 MDS patients with an equilibrium binding assay using 125I-TPO. The MDS patients had higher plasma TPO levels (7.0 +/- 9.3 fmol/ml) than 52 normal subjects (P < 0.0001). Refractory anaemia (RA) patients (n = 39) had higher plasma TPO levels than patients (n = 28) with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-t) (P = 0.0002), irrespective of similar platelet counts in these groups. The plasma TPO level correlated inversely with the platelet count in RA patients (P = 0.0027) but not in RAEB and RAEB-t patients (P = 0.7865). These data suggest that the physiological pathway for TPO production and metabolism is conserved, at least partially, in RA, but deranged in RAEB/RAEB-t. The number of TPO-R per platelet was significantly smaller in 19 MDS patients (17.5 +/- 13.3) than in normals (P = 0.0014), but similar between RA patients and patients with RAEB and RAEB-t. Further, the bone marrow megakaryocyte count, determined in 31 MDS patients, was quite similar between RA patients and patients with RAEB or RAEB-t. Thus, in addition to thrombocytopenia, a reduced platelet TPO-R number may contribute to elevated plasma TPO levels in MDS, and a regulatory pathway for circulating TPO other than platelet TPO-R and marrow megakaryocytes, such as blasts expressing TPO-R, may operate in RAEB/RAEB-t.

Blood Platelets↗
PubMed1998

Changes in tissue oxygen tension caused by contrast media injected into the femoral artery of the dog.

PURPOSE: To document changes in tissue oxygen tension as measured directly in an area perfused with contrast medium. MATERIAL AND METHODS: Changes in tissue oxygen tension in response to the injection of ionic and non-ionic contrast media into the femoral arteries were measured in the femoral adductor (proximal) and gastrocnemius (distal) muscles of 8 dogs. Amidotrizoic-acid and iopamidol were injected in two different iodine concentrations (370 mg I/ml and 185 mg I/ml respectively) and tissue oxygen tension in the proximal and distal muscles was monitored continuously using polarographic needle electrodes. RESULTS AND CONCLUSION: A transient decrease and subsequent increase of muscle tissue oxygen tension were observed after the injection. The extent of these changes depended on the concentration and osmolality of the medium. To minimize changes in peripheral tissue oxygen tension, contrast media with low osmolality and low concentration are recommended for femoral angiography.

Angiography↗
PubMed1998

Holt-Oram syndrome.

Holt-Oram syndrome (HOS) is a rare disorder characterized by congenital anomalies of the upper limbs and heart. Cardiac arrhythmias are common in patients with HOS. We successfully managed a 24-yr-old woman with HOS who underwent laparoscopic ovarian cystectomy. Potential problems in the anaesthetic management of patients with HOS are discussed.

Adult↗
PubMed1998

Efficacy of extracorporeal ultrafiltration of ascitic fluid as a treatment of refractory ascites.

BACKGROUND: Refractory ascites is recognized in patients with various conditions. Although intravenous reinjection of ascitic fluid after its filtration and concentration (IRA) is an effective method of treating this condition, many associated side-effects have been reported. We performed extracorporeal ultrafiltration of ascitic fluid (EUA) to demonstrate the efficacy and advantages of this method of treating refractory ascites. METHODS: EUA was performed in seven patients with hepatic cirrhosis (3 cases), lupus nephritis, diabetic nephropathy, and carcinomatous peritonitis (2 cases) for a total of 122 sessions. IRA was performed in three of these seven patients for a total of 12 sessions. RESULTS: The average volumes of ascitic fluid removed by EUA and IRA were 3.94+/-1.45 litres and 2.87+/-0.69 litres (mean+/-SD) respectively. Although chills and acute renal failure were recognized as complications of IRA in five and one sessions respectively, the only complication of EUA was severe intra-abdominal haemorrhage, which resolved spontaneously. In spite of rapid and massive removal of ascitic fluid (maximum 2.0 litres per 15 min), significant changes in blood pressure were not noted during EUA. In three patients (hepatic cirrhosis, lupus nephritis, and diabetic nephropathy), de novo production of ascitic fluid disappeared. In one patient with hepatic cirrhosis and chronic renal failure on haemodialysis, 67 sessions of EUA have been performed under stable conditions. Three patients (one case of hepatic cirrhosis and two cases of carcinomatous peritonitis) died of their primary diseases. CONCLUSIONS: We conclude that EUA is a useful method for the treatment of massive refractory ascites.

Adult↗