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Biomedical subjects

K Dan

Publications and source records attributed to K Dan.

At least 127 records · Page 7Linked to original sources

Assessment of therapeutic potential of interleukin 2 for myelodysplastic syndromes.

The therapeutic potential of interleukin 2 (IL-2) for myelodsplastic syndromes (MDS) was evaluated in vitro. IL-2-induced lymphokine-activated killer (LAK) cells were prepared from 38 MDS patients and 20 normal subjects. The cytotoxicity of LAK cells against K562 and Raji cell lines and MDS blasts was significantly reduced in high-risk MDS (refractory anaemia with excess blasts (RAEB), RAEB in transformation, and leukaemic transformation of MDS), but was relatively well-preserved in low-risk MDS (refractory anaemia (RA) and RA with ringed sideroblasts). Examination of the immunophenotypes of freshly-isolated lymphocytes showed that the percentage of CD4+ cells in low-risk MDS and the percentage of CD3+, CD4+ and CD8+ cell populations in high-risk MDS was significantly reduced compared with these populations in normal subjects. After cultivation with IL-2, these three cell populations were still reduced in the corresponding MDS groups and the percentage of CD3-CD56+ cells were significantly reduced in high-risk MDS. There was a positive correlation between the percentage of K562 cells lysed by MDS LAK cells and the percentage of CD3-CD56+ lymphocytes in MDS LAK cells. These aberrant lymphocyte subpopulations appeared to explain, at least in part, the reduced LAK cell cytotoxicity in MDS. These results present a possibility that IL-2 and LAK therapies are ineffective for most high-risk MDS patients, whereas they have potential value for low-risk MDS patients whose lymphocyte cytotoxicity is usually preserved.

Adult↗

Marked basophilia in acute promyelocytic leukaemia treated with all-trans retinoic acid: molecular analysis of the cell origin of the basophils.

We report a patient with acute promyelocytic leukaemia who developed marked basophilia during all-trans retinoic acid treatment. We studied genomic DNA and RNA extracted from the patient's peripheral leucocytes in order to determine the origin of the basophils. The RAR alpha rearranged band in the Southern blot analysis and a chimaeric product of PML-RAR alpha by polymerase chain reaction were strongly visible before ATRA treatment, but at the time of maximal basophilia both of them were markedly diminished. These findings suggest that the basophils which appeared during the ATRA treatment are reactive in nature rather than a leukaemic clone.

Base Sequence↗

Defective natural killer (NK) cell-mediated cytotoxicity does not imply clonal involvement of NK cells in myelodysplastic syndromes.

The clonality of purified cells was examined in 10 myelodysplastic syndromes (MDS) patients by analysing the restriction fragment length polymorphism and methylation pattern of the phosphoglycerate-kinase gene. Natural killer (NK) cell-mediated cytotoxicity was also examined. The granulocytes and monocytes were monoclonal or oligoclonal in all cases, except for the monocytes in one case. Conversely, the NK and T cells had a polyclonal pattern in most cases, including all cases who had defective NK cell-mediated cytotoxicity. The hypothesis that reduced NK cell-mediated cytotoxicity in MDS is caused by a clonal involvement of NK cells was not supported by the present study.

Adult↗

Effects of N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) on insulin and glucagon secretion in isolated perfused rat pancreas.

N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) has a structure which differs from those of other known blood glucose-lowering agents including sulfonylureas. It has been shown that oral administration of A-4166 exerts blood glucose-lowering effects in animal in vivo studies. In the present study, we investigated the effects of A-4166 on insulin and glucagon secretion at several glucose concentrations using isolated perfused rat pancreas preparations. Both 3.0 and 30 mumol/l A-4166 significantly stimulated insulin secretion as compared with basal levels at glucose concentrations of 8.0 and 11.0 mmol (p < 0.01 and p < 0.05, respectively). In contrast, glucagon secretion was not affected by administration of A-4166 up to 30 mumol/l at these glucose concentrations. At a glucose concentration of 5.6 mmol/l, neither 0.3 nor 3.0 mumol/l A-4166 produced significant changes in insulin and glucagon secretion. However, A-4166 at 30 mumol/l significantly stimulated insulin secretion and inhibited glucagon secretion as compared with basal levels (p < 0.01 and p < 0.01, respectively). We conclude that A-4166 at 3.0 and 30 mumol/l directly stimulates insulin secretion but has little effect on glucagon secretion in isolated perfused rat pancreas at glucose concentrations of 8.0 and 11.0 mmol/l. these results, taken together with previously published data, suggest that oral administration of A-4166 could be a useful strategy for stimulating endogenous insulin secretion in non-insulin-dependent diabetic patients.

Animals↗

Possible correlation of b3-a2-type bcr-abl messenger RNA defined by semiquantitative RT-PCR to platelet and megakaryocyte counts in Philadelphia-positive chronic myelogenous leukemia.

Thirty-five patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) were classified on the basis of the fusion pattern of bcr-abl mRNA determined by the reverse-transcriptase-polymerase chain reaction (RT-PCR) method. Semiquantitative assay of the bcr exon 2/abl exon 2 fused mRNA (b2-a2) and bcr exon 3/abl exon 2 fused mRNA (b3-a2) resulted in 21 patients showing b3-a2 type mRNA, seven showing b2-a2 type and seven showing coexpression. Quantification of the autoradiographic signals of amplified products was estimated using an MCID image analysis system. The relative intensity was defined as the ratio of bcr-abl signal to that of beta-actin. The relationship between the semiquantified bcr-abl mRNA and the platelet/megakaryocyte counts was analyzed. A possible correlation was found between the semiquantified b3-a2 type mRNA and the platelet (p < .05, N = 28) and megakaryocyte (p < .05, N = 13) counts of these patients. This finding suggests the possibility that b3-a2 mRNA may affect the thrombopoietic activity in Ph1-positive CML in a dose-response manner.

Autoradiography↗

[Anesthetic management of a patient with Kimura's disease].

Kimura's disease is a rare disease characterized by granuloma in soft tissues with formation of lymphoid follicles infiltrated with eosinophils. It is accompanied by peripheral eosinophilia and elevated IgE in some patients. Although most patients with Kimura's disease were Japanese, we are not aware of reports about anesthetic management of this disease. We managed a 38-year-old woman with Kimura's disease who underwent a removal of a right preauricular mass with general anesthesia using oxygen, nitrous oxide (50%), and isoflurane (0.5-1.5%). There were no anesthesia-related complications. Anesthetic management of patients with Kimura's disease is also discussed.

Adult↗

[Pediatric one-lung anesthesia with a Fogarty catheter].

One-lung anesthesia using a Fogarty catheter in pediatric patients is presented. Case 1 is an 8 year old male with coarctation of the aorta scheduled for coarctectomy. Case 2 is a 13 year old female with metastatic lung tumor scheduled for partial resection of the left upper lobe under thoracoscopic surgery. One-lung anesthesia was successfully established with a Fogarty catheter in both patients and no hypoxic episode was encountered during the one-lung anesthesia. Postoperatively, there was no evidence of atelectasis of the lung or barotrauma to the trachea or bronchus. Thus, the Fogarty catheter appears useful for pediatric one-lung anesthesia, especially when the double lumen endobronchial tubes or endobronchial blockers of smaller sizes are not available.

Adolescent↗

[Anesthesia for a patient with olivopontocerebellar atrophy].

Olivopontocerebellar atrophy (OPCA) is one of the spinocerebellar degenerative diseases. Reports of patients complicated with OPCA are scarce in anesthetic literature. We managed a 79-year-old woman with sialolithiasis of the left submandibular gland complicated with OPCA. She underwent a removal of the gland under general anesthesia using oxygen, nitrous oxide, and isoflurane (0.6-2.0%). Blood pressure decreased transiently after induction of anesthesia, but, no vasopressors were needed to maintain the blood pressure during the surgery. There were no untoward cardio-respiratory events after the surgery. Perioperative anesthetic management of patients with OPCA is also discussed.

Aged↗

Aplastic anemia with circulating erythroblasts.

Since the presence of erythroblasts (Ebl) in the peripheral blood of patients suspected to have aplastic anemia (AA) has been thought to suggest an error in diagnosis, such patients may not receive appropriate therapy promptly, with potentially fatal results. However, we recently experienced patients who had the typical features of AA except for circulating Ebl, and responded well to therapy for AA. In this study, we examined 55 untreated AA patients for the presence of circulating Ebl. Seven patients (12.7%) had circulating Ebl (at least one Ebl per 200 leukocytes counted). These seven patients showed the typical features of AA. There were no significant differences in age or hematologic parameters, including the morphology of bone marrow Ebl, between the AA patients having circulating Ebl (Ebl(+) AA) and the AA patients without Ebl. All but one of the Ebl(+) AA patients responded well to the therapy for AA. During 12.0-110.4 months of follow-up, transformation to other diseases did not occur, and all seven patients were alive. We conclude that circulating Ebl are not rare in patients who have otherwise typical features of AA, and that if such Ebl(+) AA patients are severely cytopenic, they should receive treatment for AA without delay.

Adolescent↗

[Tracheal rupture in a patient intubated with a double-lumen endobronchial tube].

We report a case of tracheal rupture associated with use of a double-lumen endobronchial tube. The patient was a 58-year-old woman with metastatic carcinoma of the right upper lung lobe. Her trachea was intubated easily with a left-sided double-lumen endobronchial tube (Broncho-Cath, #35Fr). She underwent right upper lobectomy under general anesthesia using isoflurane (0.4-1.0%) and nitrous oxide (50%) in oxygen. When the lungs were inflated before closure of the chest, an air leak at the membranous part of the trachea was detected. A tracheal rupture, beginning 3 cm above the carina and 7 cm long, was noted at the membranous part of the trachea, and the cuff protruded partially from the ruptured trachea. The trachea was sutured, and a tracheostomy was carried out. Mechanisms of tracheal rupture related to double-lumen endobronchial tubes are discussed.

Anesthesia, General↗

[Inhibition by sedatives of compensatory vasoconstriction during lumbar epidural anesthesia].

Compensatory vasoconstriction in an upper extremity during lumbar epidural anesthesia contributes to the stability of hemodynamics. We measured blood flow of an index fingertip (FBF) with laser-Doppler flowmetry, surface temperature of a middle fingertip (FT), deep body temperature of the forehead (HDT) and a big toe (BDT) by an insulated thermistor probe of zero thermal flow between skin and subcutaneous tissue, and mean arterial pressure (MAP) in 16 patients undergoing elective lower abdominal surgery under lumbar epidural anesthesia. Epidural puncture was done at L1-2 (n = 2), L2-3 (n = 8) or L3-4 (n = 6), and the initial dose of 13 +/- 1 ml (mean +/- SD) of 2% plain mepivacaine (n = 14) or 2% plain lidocaine (n = 2) was injected five minutes after the test dose of 3 ml. Five minutes after the initial injection, the hypesthesia region of cold sensation examined by alcohol absorbent cotton was T9 +/- 3 (range, T2-T12) at the upper limit and S2 +/- 2 (range, L2-S3) at the lower limit. After determination of the hypesthesia region, a combination of butorphanol 1.0 +/- 0.1 mg and midazolam 2.0 +/- 0.9 mg or diazepam 7.5 +/- 2.5 mg alone was administered intravenously. The difference between HDT and BDT decreased significantly from 6.4 degrees C (P < 0.01) at the time of test dose injection to 0.4 degrees C (P < 0.001) 20 minutes after the initial dose injection of local anesthetics. FBF showed a twofold significant increase (P < 0.01) 20 minutes after the initial dose injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Validity of non-invasive deep body thermometry to evaluate thermoregulation].

We evaluated, as an index of thermoregulation and hemodynamics, the validity of deep body thermometry that measures deep tissue temperature transcutaneously by creating an area under an insulated thermistor probe of zero thermal flow between skin and subcutaneous tissue in 27 patients undergoing cardiac surgery. Deep body temperatures (DBT) were measured at the forehead (FH) and palm (P), and the DBT gradients (DBTFH-P) were compared with simultaneously measured mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance (SVR), the gradients (TESODBTP, TRECDBTP) of the esophageal and rectal temperatures and palm DBT during a three hour period after discontinuing cardiopulmonary bypass. Among the body temperature and hemodynamics measurements, the closest linear relationship was found between DBTFH-P and TESODBTP [0.35 + 0.95 x TESODBTP (degrees C), r = 0.98, SEE = 0.45, P < 0.0001]. There were no correlations between DBTFH-P and MAP, CI and SVR. We conclude that the measurement of DBTFH-P is useful as a reliable non-invasive method of monitoring core and shell temperature to evaluate thermoregulation.

Body Temperature Regulation↗

p53 and N-ras mutations in two new leukemia cell lines established from a patient with multilineage CD7-positive acute leukemia.

Two new myeloid cell lines (K051 and K052) were established from a patient with multilineage CD7-positive acute leukemia. The K051 and K052 were established from the patient's bone marrow cells at diagnosis and at relapse, respectively. The K051 cell expressed myeloid-associated antigens (CD13 and CD33), a platelet-associated antigen (CD41), and an erythroid antigen (glycophorin A). The K052 cell expressed myeloid-associated antigens (CD13, CD14, and CD33), lymphoid markers (CD2, CD5, and CD7), and HLA-DR. Chromosome analysis of both cell lines showed a 17p- chromosome. Both cell lines were investigated for aberrations of the p53 gene and the N-ras gene. A p53 mutation detected in both cell lines consisted of a C-->T substitution in codon 248. An N-ras mutation detected only in the K052 cell consisted of a G-->C substitution in codon 13. Expression of the multidrug resistance gene (MDR1) was also investigated by the semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). MDR1-mRNA was more highly expressed by the K052 cell than the K051 cell, being equivalent to that in HEL cells. The functional MDR1-protein against vincristine was also observed, and its function was inhibited by verapamile and Cyclosporin A. The K052 cells were capable of phenotypic or morphologic differentiation after being incubated with granulocyte colony-stimulating factor, interleukin-2, phorbol 12-myristate 13-acetate, or 1,25-dihydroxy-vitamin D3. In contrast, the K051 cells responded phenotypically to retinoic acid. Thus, the K051 and K052 cell lines will be useful for investigating the cellular and molecular events in leukemogenesis and differentiation, and the mechanism of expression of the MDR1 gene.

Acute Disease↗

Alterations in the deleted in colorectal carcinoma gene in human primary leukemia.

To evaluate the role of the deleted in colorectal carcinoma (DCC) gene in leukemogenesis, we examined loss of heterozygosity (LOH) in the DCC gene in 64 primary human leukemias using Southern blot analysis and examined the expression of the DCC gene using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Allelic loss in the DCC gene was observed in two patients (6%, 2 of 35 informative cases), and expression of the DCC gene was reduced or absent in 8 of 26 (31%) patients with acute myelogenous leukemia (AML), 3 of 9 (33%) patients with acute lymphocytic leukemia (ALL), and 7 of 29 (24%) patients with chronic myelogenous leukemia (CML). Moreover, in one ALL patient with absent DCC expression at diagnosis, its expression became normal after performing chemotherapy and achieving remission. These findings suggest that inactivation of the DCC gene contributes to some instances of leukemogenesis.

Alleles↗

Intra-operative blood pressure control by prostaglandin E1 in patients with hypertension and ischemic heart disease--a multi-center study.

The purpose of this multi-center study was to evaluate the efficacy and safety of prostaglandin E1 (PGE1) administration in achieving deliberate hypotension and in treating intraoperative hypertension for patients with a history of hypertension and ischemic heart disease. PGE1 (0.08 microg.kg(-1).min(-1)) decreased systolic blood pressure from 125 +/- 29 to 106 +/- 22 mmHg (mean +/- SD) in the deliberate hypotension group (n = 158) and from 155 +/- 34 to 125 +/- 32 mmHg in the antihypertension group (n = 55). The heart rate significantly increased from 80 +/- 15 to 85 +/- 18 beats.min(-1) in the deliberate hypotension group, but was not significantly altered in the antihypertension group. The time required to obtain the desired level of blood pressure was approximately 20 min in the deliberate hypotension group. When the infusion was stopped, blood pressure returned approximately to the preinfusion level within about 20 min. No rebound hypertension was observed. PGE1 significantly increased the urine flow in patients who had a low urine flow before PGE1 infusion. Thirteen out of 213 patients (5.6%) had side effects such as excessive hypotension (1%), phlebitis (3%), and unexpected tachycardia (1%), which were alleviated gradually after discontinuation of PGE1 infusion. No dysarrhythmia and further ST segment changes in the electrocardiograms were observed. These findings suggest that PGE1 can be safely used to control arterial blood pressure during surgery in patients having preoperative hypertension and ischemic heart disease.

Journal Article↗

Effects of interleukin 2 on myelodysplastic syndromes.

To evaluate the clinical usefulness of interleukin 2 (IL-2) on myelodysplastic syndromes (MDS), the serum IL-2 level, the effect of IL-2 on the proliferation of blasts, and the cell-mediated cytotoxic effect of IL-2 on blasts were examined in MDS patients. Of 18 patients, 2 patients had an increased serum IL-2 level. Although the proliferation of blasts in most cases, including the two patients having a high serum IL-2 level, was not stimulated by IL-2, the blasts of one case apparently proliferated in response to IL-2. It was also clearly shown that IL-2-stimulated normal peripheral blood mononuclear cells (PBMNC) showed cytotoxicity against MDS blasts, whereas the PBMNC of the advanced stages of MDS were usually defective in regard to this IL-2-dependent cytotoxicity. The therapeutic usefulness of IL-2 or lymphokine-activated killer cells for MDS was not established by the present study.

Cell Division↗

Expression of the DCC gene in myelodysplastic syndromes and overt leukemia.

To evaluate the molecular events in the genome that are associated with myelodysplastic syndromes (MDS) and the development of leukemia, we investigated the expression of the deleted in colorectal carcinoma (DCC) gene by the reverse transcriptase-polymerase chain reaction (RTPCR) method in 24 MDS cases and in 7 overt leukemia cases that progressed from MDS. Expression of the DCC gene was absent or extremely reduced in 2 of the 24 MDS cases, and those 2 cases developed overt leukemia within 6 months. Moreover, in 5 of the 7 cases of overt leukemia that developed from MDS, expression of the DCC gene was absent or extremely reduced. These findings suggest that inactivation of the DCC gene may be the late event that triggers the progression of MDS to leukemia.

Adult↗