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Biomedical subjects

R Onishi

Publications and source records attributed to R Onishi.

At least 19 recordsLinked to original sources
PubMed1998

Therapy-related leukemia and myelodysplasia following oral administration of etoposide for recurrent breast cancer.

We report a high risk of therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) in patients receiving oral administration of etoposide for recurrent breast cancer. We examined 119 patients with recurrent disease. Patients were initially treated with anthracyclines, cyclophosphamide, or cisplatin with or without radiation before etoposide treatment. Etoposide was used as the final drug in most cases. Twenty-four patients were treated with the oral administration of etoposide (50 or 100 mg/day for 5-7 days at 4-week intervals). Three cases of t-AML/MDS developed among those 24 patients exposed to etoposide. In contrast, the development of t-AML/MDS was not observed in the other 95 patients not treated with etoposide. Our data suggest that there is a substantial risk of secondary leukemia with oral administration of etoposide for a prolonged period as well as i.v. schedules.

Administration, Oral↗
PubMed1998

[Extramedullary relapse in the external auditory canal in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid and autologous peripheral blood stem cell transplantation].

A 41-year-old man was given a diagnosis with of acute promyelocytic leukemia (APL) in August 1994. A chromosome analysis showed 46, XY, t(15; 17) and 47, XY, idem, +8 at that time. Because initial induction chemotherapy (BHAC-DMP) has not been successful, the patient was given 45 mg/m2 of all-trans retinoic acid (ATRA) and achieved complete remission (CR) after 26 days on this regimen. Following intensified chemotherapy, he received an autologous peripheral blood stem cell transplant (PBSCT) with high-dose busulfan and cyclophosphamide in April 1995. Competitive RT-PCR for PML-RAR alpha mRNA did not find any of APL cells in the collected stem-cell fraction. Although the patient remained in CR without therapy, a myeloblastoma was found in his left external auditory canal in August 1996. Recurrence in bone marrow, moreover, was discovered the following month. A chromosome analysis of bone marrow cells showed 47, XY, t(15; 17), +8 at this time. Thus, the extramedullary relapse developed after autologous PBSCT. This case provides information linking ATRA to the development of extramedullary relapse in patients with APL.

Adult↗
PubMed1997

Sequential interphase FISH analysis of m-BCR/ABL chimeric gene-positive cells in Ph-positive acute myeloid leukemia.

We report a case of Philadelphia (Ph)-positive AML in which interphase fluorescence in situ hybridization (FISH) analysis was performed from diagnosis throughout the course of therapy using major (M-) breakpoint cluster region (BCR)/minor (m-) BCR and ABL cosmid probes. We also investigated the existence of the M-BCR or m-BCR at the RNA or DNA level by the reverse transcriptase polymerase chain reaction and Southern blot analysis, respectively. Complete remission with a normal karyotype was achieved after several regimens of chemotherapy and peripheral blood stem cell transplantation (PBSCT), but relapse occurred and his cells became 100% Ph-positive. We detected the m-BCR/ABL fusion gene by interphase FISH analysis using an m-BCR/ABL translocation probe, and found that FISH analysis was useful for classifying the BCR, identifying minimal residual disease, and for predicting imminent relapse after chemotherapy and PBSCT.

Acute Disease↗
PubMed1996

Ectopic adrenocorticotropin syndrome associated with undifferentiated carcinoma of the colon showing multidirectional neuroendocrine, exocrine, and squamous differentiation.

We report a rare case of ectopic ACTH syndrome associated with undifferentiated carcinoma of the ascending colon. A 62-year-old woman developed hypokalaemia and metabolic alkalosis associated with markedly elevated serum cortisol and plasma ACTH levels. High-dose dexamethasone (8 mg/day) did not suppress increased urinary 17-hydroxycorticosteroid and 17-keto-steroid excretion. Barium enema and abdominal computerised tomography showed a Borrmann II type tumour in the ascending colon, multiple metastatic nodules in the liver and bilateral enlargement of the adrenal glands. Histological examination of the resected primary colon cancer and metastatic liver tumour showed undifferentiated carcinoma with areas of distinct neuroendocrine, exocrine, and squamous differentiation. ACTH production by the tumour was confirmed by radioimmunoassay and immunohistochemistry. This is a unique case report of carcinoma of the colon with distinct multidirectional differentiation causing ectopic ACTH syndrome.

ACTH Syndrome, Ectopic↗
PubMed1996

Mediastinal lymphangiomas in adults: CT findings.

Mediastinal lymphangioma is rare in adults, and there are few reports of their computed tomographic (CT) findings. We present the CT results in three cases of mediastinal lymphangioma. One showed a well-defined, multilocular, water-density mass enveloping mediastinal structures, without their displacement or compression; one presented as a well-defined, homogeneous, water-density mass in the right paratracheal region; and one was associated with hemorrhage into cysts and a significant increase in size over 5 years. CT is useful for diagnosis and evaluation of the extent or contents of mediastinal lymphangiomas.

Adolescent↗
PubMed1994

Hemophagocytic syndrome in a patient with rheumatoid arthritis.

A 63-year-old female, who had been diagnosed with rheumatoid arthritis (RA) 3 years previously, was admitted due to progressive pancytopenia, lymphadenopathy, fever, and weight loss. The physical and laboratory findings fulfilled all of the American Rheumatism Association (ARA) revised criteria for RA. Her bone marrow aspirate revealed a decreased nuclear cell count (1.8 x 10(4) microliters) and megakarocyte count (0/microliter), and macrophages phagocytizing blood cells (4%), indicating the presence of hemophagocytic syndrome. The serological tests for several viruses revealed no obvious viral etiology. However, a slight Epstein-Barr virus (EBV) reactivation could not be excluded. Administration of 40 mg prednisolone daily improved her abnormal hematological findings and immunological laboratory parameters. This is a case of RA accompanied by hemophagocytic syndrome, which has not been reported previously as a complication of RA.

Arthritis, Rheumatoid↗
PubMed1993

Experimental and predicted dual oximetry variability.

OBJECTIVE: We wished to determine whether the individual bias (mean difference) and precision (standard deviation of the difference) values of 2 variables, arterial oxygen saturation (SaO2) and mixed venous oxygen saturation (SvO2), could be used to predict the bias and precision values of the combined dual oximetry variable (SaO2-SvO2). METHODS: We simultaneously measured SaO2 by pulse oximetry and arterial blood gas co-oximetry and SvO2 by fiberoptic reflectance oximetry pulmonary artery catheter and venous blood gas co-oximetry in 238 data sets from 55 patients. Three different methods were used to predict the standard deviation of the difference of (SaO2-SvO2) [s delta(SaO2-SvO2)]: simple sum, root mean square (RMS) error, and RMS error with correction term. We derived the equation for the RMS error with correction term because initial results showed that the simple sum and RMS error methods did not predict s delta(SaO2-SvO2) well. The correction term accounts for the non-independence of simultaneous SaO2 and SvO2 measurements. RESULTS: The observed overall bias of the SaO2, SvO2, and (SaO2-SvO2) measurement methods were 0.17, -1.76, and 1.94, respectively. The observed overall s delta(SaO2-SvO2) of the (SaO2-SvO2) measurement method was 5.12. The simple sum method overestimated the actual s delta(SaO2-SvO2) by 38%, the RMS error method differed from the actual s delta(SaO2-SvO2) by 3%, and the RMS error with correction term method matched the actual s delta(SaO2-SvO2). CONCLUSION: The bias of a (SaO2-SvO2) measurement method is simply the bias of the SaO2 measurement method less the bias of the SvO2 measurement method. s delta(SaO2-SvO2) is best predicted by the derived equation, RMS error with correction term. The same principles and equations also apply to other situations in which 2 variables with the same dimensions are combined into 1 variable, such as (PaCO2-EtCO2) gradients and perfusion-pressure gradients. Although the difference between the s delta(SaO2-SvO2) predicted by the RMS error equation and the derived RMS error equation with correction term was small, the difference may be significant for other combined variables.

Oximetry↗
PubMed1993

Prognosis of mechanically ventilated patients.

In this Department of Veterans Affairs cooperative study, we examined predictors of in-hospital and 1-year mortality of 612 mechanically ventilated patients from 6 medical intensive care units in a retrospective cohort design. The outcome variable was vital status at hospital discharge and after 1 year. The results showed that 97% of patients were men, the mean age was 63 +/- 11 years (SD), and hospital mortality was 64% (95% confidence interval, 60% to 68%). Within the next year, an additional 38% of hospital survivors died, for a total 1-year mortality of 77% (95% confidence interval, 73% to 80%). Hospital and 1-year mortality, respectively, for patients older than 70 years was 76% and 94%, for those with serum albumin levels below 20 grams per liter it was 92% and 96%, for those with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 35 it was 91% and 98%, and for patients who were being mechanically ventilated after cardiopulmonary resuscitation it was 86% and 90%. The mortality ratio (actual mortality versus APACHE II-predicted mortality) was 1.15. Conclusions are that patient age, APACHE II score, serum albumin levels, or the use of cardiopulmonary resuscitation may identify a subset of mechanically ventilated veterans for whom mechanical ventilation provides little or no benefit.

Aged↗
PubMed1992

Phorbol esters up-regulate p55 and down-regulate p75 expression of interleukin-2 receptors in human T cells.

We examined the effects of phorbol esters on the expression of interleukin 2 receptors (IL-2R) in T cell clones. By flow cytometric analysis, we found that phorbol esters up-regulated IL-2R p55 expression, while they down-regulated p75 expression. The expression of IL-2R p55 in T cell clones treated with phorbol esters showed an initial transient and marginal decrease, which was followed by a progressive increase after 6 h of incubation. On the other hand, the expression of IL-2R p75 progressively decreased to a minimum plateau level. Down-regulation of p75 was also revealed in cells treated with diacylglycerols instead of phorbol esters, but there was no up-regulation of p55 in these cells. Moreover, in the presence of cycloheximide, phorbol esters down-regulated p75 expression but did not up-regulate p55 expression. Therefore, it seems that a transient activation of protein kinase C (PKC) is sufficient to down-regulate p75, but not to up-regulate p55, and that a novel protein synthesis is required to increase p55 expression.

Down-Regulation↗
PubMed1991

Interleukin-3-induced downregulation of the expression of interleukin-2 receptor beta chain in human T cells.

We examined the effect of interleukin-3 (IL-3) on human CD4+ cloned T cells, P607 and 1C2. By flow cytometric analysis, we found that IL-3 downregulated the surface expression of IL-2 receptor (R) beta chain in a dose-dependent manner but had little effect on that of IL-2R alpha chain. A simultaneous 125I-labeled IL-2 binding assay showed a decrease in the number of high-affinity, but not of low-affinity, IL-2Rs by IL-3. The downregulation of the IL-2R beta chain began 3 hours after culture initiation, increased further thereafter, and was completely inhibited by anti-IL-3 antibodies. Expression of mRNA for either alpha or beta chain was not reduced by IL-3, and this suggests that the reduction of surface beta chain expression was not caused by the reduction of beta chain mRNA. IL-3-accelerating internalization of IL-2R beta chain appeared to be one of the mechanisms for IL-3-induced downregulation of surface IL-2R beta chain expression. IL-3 alone increased the proliferation of T-cell clones but decreased the existing increment of their proliferation by IL-2. Accordingly, IL-3 may be one of the factors acting as a liaison between the hematopoietic and immune systems.

Blotting, Northern↗
PubMed1991

IL-4 down-regulates IL-2 receptor p75 by accelerating its endocytosis.

We examined the effects of interleukin 4 (IL-4) on the expression of IL-2 receptor p75 (IL-2R p75) or beta chain on various human T cells. IL-4 promptly down-regulated surface IL-2 receptor (IL-2R) p75 in these cells. Although IL-2-induced IL-2R p75 down-regulation was seen more quickly, IL-2 did not contribute to the process of the IL-4-induced decrease of IL-2R p75. Northern blotting revealed that IL-4 did not reduce the expression of IL-2R p75 mRNA. Studies using Pronase E, which digests cell surface IL-2R p75, or brefeldin A, which blocks intracytoplasmic protein transport from endoplasmic reticulum to the Golgi apparatus, suggest that IL-4-induced IL-2R p75 down-regulation is controlled after IL-2R p75 is expressed on the cell surface. We found that IL-4 accelerated the endocytosis of IL-2R p75, which was monitored by [125I]Mik-beta 3 monoclonal antibody that recognizes non-IL-2-binding epitope on IL-2R p75. These findings demonstrate that IL-4 down-regulates IL-2R p75 mainly by accelerating its endocytosis.

Cell Line↗
PubMed1990

Selective expression of the p70 subunit of the interleukin-2 receptor on lymphocytes from patients with infectious mononucleosis.

The lymphocytosis manifested in infectious mononucleosis (IM) during acute phase is ascribed to a reactive expansion of CD8+ T lymphocytes caused by Epstein-Barr virus (EBV)-infected B lymphocytes. Expression of HLA-DR antigen on IM lymphocytes suggests that these T lymphocytes are somehow activated in vivo. In the present study, we analyzed the interleukin-2 (IL-2) receptor expression on lymphocytes from six patients with acute IM. Radiolabeled IL-2 binding assay revealed that IM lymphocytes from all patients examined had a considerable number of IL-2 binding sites with an intermediate affinity, although they did not express the IL-2 receptor recognized by anti-Tac antibody (p55). The number of binding sites (1,070 to 4,600 sites per cell) was larger than that of a normal, resting T lymphocyte-enriched population (650 sites per cell). Furthermore, IM lymphocytes showed marked proliferative responses to higher concentrations of IL-2, which were almost completely blocked by an anti-p70 IL-2 receptor antibody, indicating that their IL-2 receptor is a functional receptor. The results of an affinity cross-linking study seem to indicate that the IL-2 receptor expressed on IM lymphocytes is p70, the second chain of the IL-2 receptor distinct from p55. Flow cytometric analysis following immunofluorescent staining with anti-p70 IL-2 receptor antibody confirmed p70 expression on CD8+ HLA-DR+ lymphocytes. These data suggest that p70 IL-2 receptor expression is involved in the immune response triggered by EBV infection.

Acute Disease↗
PubMed1990

Treatment decisions in "white coat" hypertension: do we need the whole 24 hours?

Twenty-four hour ambulatory blood pressure monitoring (24BP) is an emerging technology used to further evaluate elevated blood pressure readings obtained during office visits. We wondered whether a less costly approach than 24BP would lead clinicians to similar treatment decisions. Eleven faculty general internists sequentially evaluated sample patients' office blood pressure readings, four intermittent blood pressures (IBP), and 24-hour ambulatory blood pressure reports and made treatment decisions at each step. This yielded 187 "cases," in 173 of which the physicians were able to make treatment decisions. We found that addition of either IBP or 24BP to office readings did change treatment decisions (P less than .0001), but the changes brought about by IBP and 24BP were of statistically similar magnitude. We suggest that during clinical trials designed to evaluate the value of 24-hour ambulatory blood pressure monitoring in various clinical situations, simpler and perhaps less costly technology should be concurrently evaluated as an alternative.

Ambulatory Care↗
PubMed1990

Interleukin-2 receptor beta-chain (p70-75) expressed on leukemic cells from adult T cell leukemia patients.

To determine whether the interleukin-2 receptor (IL-2R) beta-chain (p70-75) is expressed on leukemic cells from patients with adult T cell leukemia (ATL) as well as alpha-chain (p55, Tac), we performed radiolabeled interleukin-2 (IL-2) binding assay, chemical crosslinking of radiolabeled IL-2 and flow cytometric analysis using a newly-developed anti-IL-2R beta-chain antibody. The results showed that leukemic cells from all the 12 ATL patients we examined expressed the IL-2R beta-chain together with the alpha-chain whereas there was no detectable beta-chain expression on unstimulated peripheral blood CD4(+) T cells from healthy volunteers. Southern blot analysis revealed that this abnormal expression was not caused by the structural change of IL-2R beta-chain gene. Though leukemic cells from all ATL patients examined expressed high-affinity IL-2Rs, leukemic cells from only 25% of all ATL patients proliferated in response to IL-2. These results showing abnormal expression of IL-2R beta-chain on leukemic cells from ATL patients (ATL cells) suggest a close association between HTLV-I infection and abnormal beta-chain expression as well as alpha-chain expression.

Aged↗
PubMed1989

Thoracic bioimpedance and Doppler cardiac output measurement: learning curve and interobserver reproducibility.

Nine previously untrained health professionals learned to measure cardiac output (Qt) by suprasternal continuous-wave Doppler ultrasound (QtDopp) and by thoracic bioimpedance (Qtbi). Each received standardized written, videotaped, and individual instruction. First the novice, then the reference examiner, measured QtDopp or Qtbi in triplicate in an adult male subject. The reference examiner was blind to the novice measurements and the novice was not informed of the reference measurements. Each novice repeatedly measured QtDopp or Qtbi in different subjects until the mean novice QtDopp or Qtbi was within 10% of the corresponding mean reference measurement in three of four consecutive subjects. The novice observers required an average of 12.9 +/- 3.5 trials to learn to measure QtDopp, and an average of 8.4 +/- 4.5 trials to learn to measure Qtbi. The likelihood of novice agreement with the reference improved with experience. The same degree of intraobserver variability as reported for Qt measured by thermodilution (coefficient of variance less than or equal to 10%) was achieved with Qtbi in 150 (99%) of 152 triplicate measurements and QtDopp in 216 (97%) of 222 triplicate measurements. More importantly, interobserver agreement (within 10%) was achieved with both Qtbi and QtDopp. Reproducible noninvasive Qt measurement will allow these techniques to be used to monitor trend changes in Qt.

Cardiac Output↗
PubMed1989

Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome.

Chronic fatigue syndrome is a recently defined entity for which clinical criteria were proposed by the Centers for Disease Control, Atlanta, Ga. A frequently advocated treatment in Southern California is an injectable solution of bovine liver extract containing folic acid and cyanocobalamin (LEFAC). We conducted a double-blind, placebo-controlled, crossover trial of intramuscular LEFAC in 15 patients who met the Centers for Disease Control criteria for chronic fatigue syndrome. Although patients responded to placebo and LEFAC by several criteria of functional status, no significant difference was apparent between response to placebo and that to LEFAC. The placebo response appeared to be strong.

Adult↗
PubMed1988

Characteristics of the IL-2 receptor expressed on large granular lymphocytes from patients with abnormally expanded large granular lymphocytes. Implication of a non-Tac IL-2-binding peptide.

Large granular lymphocytes (LGL) from four patients with abnormally expanded LGL in the peripheral blood were studied regarding their receptor for IL-2. LGL from none of the cases examined expressed Tac Ag, an Il-2R glycoprotein recognized by anti-Tac mAb. However, 125I-labeled IL-2 binding experiments demonstrated that 1400 to 2800/cell IL-2 binding sites with a single affinity (K: 0.46-1.4 nM) were expressed on LGL from the four patients. The affinity was not high but about 10-fold higher than that of the low affinity IL-2R expressed on activated normal T lymphocytes. Furthermore, LGL from the four patients proliferated in response to higher concentrations of IL-2 and these responses were not inhibited by an excess amount of anti-Tac antibody. 125I-Labeled IL-2 cross-linking studies performed in two cases revealed the predominant expression of an IL-2 binding molecule with an estimated Mr of 70,000 to 75,000. After the culture with IL-2 for 48 h, expression of a small amount of Tac Ag (p55) was induced on LGL in at least three cases. These data strongly suggested that the IL-2R expressed on LGL is functional and identical to the p70, a novel IL-2 binding peptide that has been recently identified and speculated to form the high affinity IL-2R in association with the p55.

Adult↗