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Biomedical subjects

F Komatsu

Publications and source records attributed to F Komatsu.

At least 37 records · Page 2Linked to original sources
PubMed1998

[High dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) For advanced testicular cancer].

Five patients with metastatic testicular cancer of advanced extent according to the Indiana University criteria were enrolled into this study. All tumors were non-pretreated non-seminomas. Initially all patients were treated with standard dose etoposide, ifosfamide and cisplatin (VIP) regimen. The response of two cycles of VIP was evaluated by tumor markers and diagnostic imagings. Two of the five patients showed a good response to VIP and subsequently achieved a pathological complete response (pCR) following surgical resection of residual masses after 3 or 5 courses of VIP. However, they suffered from severe myelosuppression and underwent peripheral blood stem cell transplantation (PBSCT) following the final course of VIP. The remaining three patients unlikely to be cured by VIP underwent chemotherapy consisting of high dose ICE:ifosfamide (6-10 g/m2 over 4days) carboplatin (1,500 mg/m2 over 4 days), etoposide (1,600-2,400 mg/m2 over 4 days) combined with PBSCT. This regimen resulted in one partial response (PR) with marker-negative and two PR with marker-positive. Residual masses were removed in all three patients and viable tumor cells were found in two. Of the five patients enrolled, four patients (80%) remain disease-free with minimal follow-up of 20 months, and the remaining one died of cancer 10 months after PBSCT. No serious side effects or complications were encountered. This study shows that standard dose induction therapy of VIP followed by early salvage chemotherapy of high dose ICE with PBSCT is well tolerated and effective in the treatment of advanced poor-risk testicular cancer.

Adult↗
PubMed1998

Relationship between antibody-dependent cell-mediated cytotoxicity due to anti-HTLV-1 and negative signal of major histocompatibility complex class I antigens on adult T-cell leukemia cell lines.

Natural killer (NK) cells possess two types of cytotoxic activity: natural killer cytotoxicity (NKC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The NKC is regulated by the negative signal of the NK receptor, which recognizes major histocompatibility complex (MHC) class I antigens. However, it is not known whether or not the negative signal influences the ADCC. In this study, the relationship of the ADCC and negative signal was investigated. As target cells, adult T-cell leukemia (ATL) cell lines were used. When the target cells were treated with an anti-human T-lymphotropic virus type-1 (anti-HTLV-1) antibody, they were killed by the NK cells by means of the ADCC (ADCC/anti-HTLV-1). The killing levels were parallel with the cell surface HTLV-1 antigenicity. However, when these cells lines were treated with an anti-HLA, the ADCC (ADCC/anti-HLA) showed inverse correlation with the HLA antigenicity. Furthermore, when HLA polymorphic and monomorphic determinants of these target cells were blocked by F(ab')2 fragments of the anti-HLA and W6/32, the ADCC/anti-HLA was enhanced, but the ADCC/anti-HTLV-1 was not enhanced. These results suggest that the ADCC/anti-HLA may have an intimate relationship with the MHC class I antigens. The ADCC/anti-HLA may be suppressed by the negative signal. On the other hand, the ADCC/anti-HTLV-1 may have no relationship with the class I antigens and the negative signal may have no influence against the ADCC/anti-HTLV-1. The biological mechanism of this difference remains to be investigated.

Adult↗
PubMed1998

A lymphokine-activated killer (LAK)-resistant cell line, and low expression of adhesion molecules LFA-3 and VCAM-1 on its cell surface.

Tumor cell lines are generally killed by lymphokine-activated killer (LAK) cells. In this study, however, we report a LAK-resistant cell line, OKM-2T. The OKM-2T is an adult T-cell leukemia (ATL) cell line, and was compared to other ATL cell lines and non-ATL cell lines. The LAK cells were generated from healthy volunteers. Cell surface markers were determined by a flow cytometry test. The ATL and non-ATL cell lines were killed by the LAK cells, markedly or moderately. However, the OKM-2T was scarcely killed. The adhesion tendency of the OKM-2T to the LAK cells was preserved at the same level as that of the other cell lines, whereas the OKM-2T showed low levels of adhesion molecules CD58 (LFA-3), CD86, and CD106 (VCAM-1). We determined blocking tests using specific antibodies. Anti-CD58 blocked the LAK lysis. Anti-CD54 and anti-CD106 enhanced the blocking effect of the anti-CD58; anti-CD86 did not show such an effect. These results suggest that the low expression of CD58 in the OKM-2T may have an intimate relationship with LAK resistance, and that the low expression of CD106 may also be responsible for it, in part.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1997

Comparison of natural killer (NK) sensitivities of two tumor cell lines established from a cancer patient before and after radiation therapy.

Major histocompatibility complex (MHC) class I positive tumor cells are generally resistant to natural killer (NK) cells. In this report, we compared the NK sensitivities of tumor cell lines H41 and H42, which were established from a cancer patient at surgery. H41 was established before radiation therapy and H42 was established after the radiation therapy in 1985. H41 was resistant to NK cells, whereas H42 was NK-sensitive. Both cell lines reacted with W6/32, which is an antibody to the HLA common epitope determinant. However, H42 did not react to anti-HLA-locus-specific antibodies, although H41 reacted to them. When these cell lines were treated with interferon-gamma, H41 showed an increase in HLA-locus-specific antigenicity, whereas H42 did not show such a tendency. This suggests that there may have been interference in the expression of the HLA-locus-specific determinants on H42. Therefore, it was assumed that the NK sensitivity of H42 may be due to depression of an HLA-locus-specific determinant, and this depression may be related to the radiation therapy. The patient recovered from the disease after the radiation therapy and the last surgery. He is now in a tumor-free state. We propose that his recovery may be related to the conversion of the tumor cells from NK-resistant to NK-sensitive.

Carcinoma, Transitional Cell↗
PubMed1997

Incidence of electrocardiographic changes during cytapheresis using an intermittent flow centrifuge, haemonetics V50 and a continuous flow centrifuge, AS104.

Electrocardiographic (ECG) monitoring was performed during cytapheresis and the incidence of ECG changes was compared between methods of intermittent flow centrifugation using the Haemonetics V50 with apheresis donors and continuous flow centrifugation with the AS104 for peripheral blood stem cell (PBSC) collection from patients. ST depression, inverted T wave and other ECG changes were found in 49 (14.3%) of the 342 cytaphereses carried out by the intermittent flow centrifugation method and in 8 (4.7%) of the 169 PBSC collections by the continuous flow centrifugation method. This difference was significant (P < 0.05). The hemodynamic changes in the procedure with the AS104 seem to be small. This is considered to be important for prevention of serious ST and T wave changes.

Blood Component Removal↗
PubMed1997

Efficient collection of peripheral blood stem cells using the Fresenius AS104 in chronic myelocytic leukemia patients with very high numbers of platelets.

For chronic myelocytic leukemia patients with very high numbers of platelets, we describe an efficient method for the collection of peripheral blood stem cells (PBSC) using the Fresenius AS104 cell separator. In these patients, it is difficult to collect a sufficient number of PBSC, due to the platelet band interfering with the machine's red cell interface sensor. We, therefore, tried a manual adjustment of the device. The collection phase was set automatically. When the whole blood began to separate into the red cell layer and plasma (plus mononuclear cell) layer, the red cell interface setting of "7:1" was changed to "OFF," and the plasma pump flow rate was controlled manually in order to locate the interface position 1 cm from the outside wall of the centrifuge chamber. After the collection phase, the procedure was returned to the automatic setting. By repeating this procedure, we were able to collect large numbers of PBSC.

Cytapheresis↗
PubMed1997

Extracorporeal shock wave lithotripsy-induced renal laceration.

After extracorporeal shock wave lithotripsy (ESWL), perinephric hematomas, while uncommon, are a serious complication involving the risk of blood transfusion and subsequent impairment of renal function. We report a rare case of ESWL-induced renal laceration in which an expanding retroperitoneal hematoma required blood transfusion but was treated successfully without surgical intervention.

Hematoma↗
PubMed1997

The analysis of steroidogenic activity in non-hyperfunctioning adrenocortical adenoma.

The steroidogenic activities in non-hyperfunctioning adrenal adenoma (NHFA) have not yet been fully examined. Steroid content both in adenoma and its non-tumorous adjacent adrenal tissue was measured by the HPLC system in 8 cases of NHFA and 2 cases of preclinical Cushing's syndrome (PCS). Activities of cytochrome P450c17alpha, P450c21, P450c11beta, P450c18 and aldosterone-synthesizing enzyme (P450aldo) were also determined by the enzyme reconstitution system. Steroid content in NHFA varied but no significant difference was seen between NHFA and normal control adrenals. Activities of all P450s except P450aldo were confirmed in NHFA, but they were almost equivalent to those in normal control adrenals. As no significant difference between NHFA and normal controls was observed in either steroid contents or P450s activities, the steroidogenic activity of NHFA is considered to be comparable to that of normal adrenals.

Adenoma↗
PubMed1997

ACTH-independent macronodular adrenocortical hyperplasia (AIMAH): report of two cases and the analysis of steroidogenic activity in adrenal nodules.

We report clinical findings and steroidogenic activities in adrenal tissues in 2 cases of AIMAH. Endocrine studies revealed an undetectable level of plasma ACTH and a diminished circadian rhythm of plasma cortisol. A significant increase in plasma cortisol levels in response to ACTH stimulation was observed in both cases. After the administration of metyrapone in one case, urinary excretion of 17-hydroxycorticosteroid (17-OHCS) significantly increased, although the plasma ACTH level did not respond. Computed tomography showed large masses in both adrenal glands, and bilateral uptake was identified on adrenal scintigraphy. The totals for the bilateral adrenal glands were 98 g and 105 g, respectively, and the left adrenal was larger than the right in both cases. Steroid content in the nodules measured by high performance liquid chromatography (HPLC) showed that the cortisol content was definitely lower than that in cortisol-producing adenoma (CPA) and even in normal adrenals. The activities of cytochrome P450c17, P450c21 and P450c11 were evaluated in one case, and all of them were reduced in the nodules. Especially that of P450c17 was remarkably reduced. These data suggest that cortisol production in AIMAH is inefficient, and that the cause of Cushing's syndrome may be related to the marked increase in the number of cells or bulk of the tumor.

17-Hydroxycorticosteroids↗
PubMed1996

Transient depression of LWa antigen with coincident production of anti-LWa repeated in relapses of malignant lymphoma.

Three years ago, a 71-year-old female was admitted because of general lymphadenopathy. She had been on medication for hypothroidism, but had no history of pregnancy or blood transfusion. T-cell lymphoma was found. Since then, she has been treated with intermittent chemotherapy. The patient's LWa antigen was depressed during two relapses of the lymphoma and anti-LWa was detected simultaneously on both occasions. When she entered remission after therapy, her LW phenotype converted from LW(a-) to LW(a+), and this was accompanied by the disappearance of anti-LWa. This suggests that LW(a-) was a transient phenotype. In the first relapse, a total of 8 units of D- LW(a+) packed red cells and 20 units of platelets were transfused during 1 month without any haemolytic reaction. In these relapses, nonhaemolytic anaemia, hyper-gamma-globulinaemia and remarkable bone-marrow infiltration with lymphoplasma cells were recognized. She also possessed antithyroglobulin and antimicrosomal antibodies; however, these autoantibodies did not change with the relapses. These results suggests that the recurrent depressions of LWa may be closely related to the underlying disease.

Aged↗
PubMed1996

Lymphokine-activated killer cells can discriminate CD34+ leukemia cells from normal hematopoietic progenitor cells.

The ability of lymphokine-activated killer (LAK) cells to discriminate between CD34+ leukemia cells and hematopoietic progenitor cells was investigated. As effector cells, CD4(-)-LAK generated from a CD4- subset of allogeneic peripheral blood lymphocytes were used. The target cell samples were obtained from peripheral blood stem cell (PBSC) collections. Detection of residual tumor cells was performed using a polymerase chain reaction (PCR) technique for chimeric bcr/abl messenger RNA. When PBSC were obtained from patients with seminoma and lung cancer, treated with the CD4(-)-LAK for 12 h and the CD34+ cells were isolated, colony formation (CFU-GM) by these cells was preserved. When PBSC were obtained from a patient with PCR-positive acute lymphocytic leukemia and treated with the CD4(-)-LAK for 3 h, reexamination showed conversion to PCR negativity. Furthermore, when the CD34+ cells isolated from the negative converted PBSC were cultured, they still exhibited colony formation. These results suggest that the CD4(-)-LAK can kill the CD34+ leukemia cells, discriminating from the normal hematopoietic progenitors.

Antigens, CD34↗
PubMed1996

Usefulness of lymphokine-activated killer cells generated from bone marrow mononuclear cells for the purging of residual tumor cells in peripheral blood stem cell graft.

Lymphokine-activated killer (LAK) cells were generated from bone marrow mononuclear cells (BM), and the usefulness of the BM-LAK for purging of residual tumor cells in autologous peripheral blood stem cell (PBSC) graft was determined. The BM and peripheral blood lymphocytes (PBL) were obtained from the same bone marrow donors. The BM-LAK and PBL-LAK were generated by incubation with interleukin-2 for 7 days. The BM-LAK demonstrated higher killer activity against a lymphoma cell line Raji than the PBL-LAK. The BM-LAK also had a higher percentage of CD4-CD8-CD16+ cells than the PBL-LAK, which suggests that their high killer activity is related to these cells. The BM-LAK did not show any killer activity against the PBSC graft. However, they killed tumor cells which contaminated the PBSC graft, and in particular, killed chimeric bcr/abl messenger RNA-positive residual leukemic cells. These results suggest that the BM-LAK may be applicable for purging. As the BM-LAK possess higher killer activity than the PBL-LAK, they may be more useful than the PBL-LAK.

Base Sequence↗
PubMed1996

Preclinical Cushing's syndrome: report of four cases and analysis of steroid contents in adenomas.

We report 4 cases of preclinical Cushing's syndrome (PCS) that were discovered incidentally by computed tomography (CT) as adrenal incidentalomas. Routine endocrine examinations revealed a suppressed plasma ACTH level. A final diagnosis was made by means of precise endocrine assessments and adrenal scintigraphy with radiolabelled iodocholesterol. Although endocrine data varied, the positive accumulation of radioisotope in the adrenal tumor, with nonvisualization of the contralateral side, was observed in all cases. Endocrine studies and analyses of steroid contents in tumors by HPLC suggested that subtypes or heterogeneous forms of this disease entity may exist. One type shows small tumors with relatively elevated cortisol production, and a disturbed diurnal rhythm and suppression of plasma cortisol with dexamethasone (DXM). The other type showed large tumors with weak-to-average cortisol production, and the diurnal rhythm of cortisol was preserved.

17-alpha-Hydroxyprogesterone↗
PubMed1995

Natural killer (NK) and lymphokine-activated killer (LAK) activities in a patient who recovered from cancer, and the characteristics of LAK cells generated from CD4-CD8- and CD8+ peripheral blood lymphocytes.

The natural killer (NK) and lymphokine-activated killer (LAK) activities of a patient who recovered from bladder transitional cell carcinoma were determined. The patient was diagnosed in 1980 and repeated several therapies until 1986. Since 1987, he has been in a tumor-free state. Recently, very high NK and LAK activities were found. The NK activity was recognized not only against the NK-sensitive cell line K562, but also against NK-unsensitive Raji and Daudi cell lines and against autotumor cell line H41. The percentage of CD16+ in peripheral blood lymphocytes (PBL) was 52.9%, the CD8+CD16+ was 26.3%, and the CD4-CD8-CD16+ was 26.6% (17.5, 5.4 and 12.1% in healthy blood donor (control), respectively). Because the patient had large numbers of CD4-CD8- cells in the PBL, CD4-CD8- LAK were generated from them. The CD4-CD8- LAK cells exhibited extremely high killer activity, whereas the CD8+ LAK cells generated from the CD8+ cells showed a low level of killer activity. These results suggest that the tumor-free condition of this patient may be related to these high killer activities. In this patient, several cytokines were also determined, although the results were not completely interpreted.

CD8-Positive T-Lymphocytes↗
PubMed1995

[Natural killer (NK) and lymphokine-activated killer (LAK) activities of a patient recovered from bladder cancer, and the characteristics of LAK cells generated from lymphocyte subsets].

NK and LAK activities of a patient who recovered from bladder transitional cell carcinoma were determined. He was diagnosed in 1980 and operations, radiations and chemotherapies were repeated until 1986. Since 1987, a relapse has not been recognized, and he is now in a tumor free state. Recently, his very high NK and LAK activities were found. The percentage of CD 16+ in his peripheral blood lymphocytes (PBL) was 52.9%, the CD 4- CD 8- CD 16+ was 26.6% (17.5% and 12.1% in control, respectively). It seems likely that his tumor free condition may be related to these high killer activities. As a high number of CD 4- CD 8- cells were included in his PBL, it was possible to generate a CD 4- CD 8(-)-LAK and compare it with the CD 8(+)-LAK. The CD 4- CD 8(-)-LAK exhibited higher killer activity which was maintained for a long period of the culture, and a strong adherence property against the cultured tumor cells. Whereas, the CD 8(+)-LAK did not show such a high level of killer activity which decreased after two weeks into the culture. However, the CD 8(+)-LAK in this patient demonstrated higher killer activity against the auto-tumor cell line compared to what occurred with the control. A type of specific killing against auto-tumor cells may be contained in his CD 8(+)-LAK, although the MHC-restrictive killing was not confirmed. It remains unclear why the killer activities increased in this patient.

CD4 Antigens↗
PubMed1993

[Analysis of corticoids in adrenal glands by high performance liquid chromatography (HPLC)].

The HPLC system was used to separate and measure 10 kinds of corticoids in adrenal tissues. Calibration curves were drawn as straight lines that ranged from 1.25 to 20ng, or 1.25 to 200ng by peak area calculated with the chromatointegrator. The samples for the assay were extracted from homogenized tissues and treated with methanol to remove non-steroidal contaminants which may interfere with the ultraviolet absorption monitor. The recovery rate during the assay procedure was calculated using testosterone as the internal standard, because testosterone was not detected in any adrenal tissue examined in the present study. Contents of corticoids were measured in normal adrenal glands obtained during radical nephrectomy for renal cancer and in functioning adrenal adenomas. Steroid levels in the adrenal glands and tumors have been measured by radioimmunoassay until now, and the data obtained in the present study were compared with those in previous reports. Main steroids in normal adrenals were cortisol (F) and corticosterone (B), and there were certain amounts of 11-deoxycortisol (S), 11-deoxycorticosterone (DOC) and precursor steroids. 11 beta-hydroxy-androstenedione was the main androgen in the adrenal gland. Mineralocorticoids other than B and DOC were very low in the normal adrenals. There was a certain balance between the production of cortisol and corticosterone in normal adrenals. In functioning adenomas, the levels of F, B and aldosterone, and F to B ratios (F/B) varied according to their biological features. Although with the HPLC system it was possible to obtain the production balance of each steroid clearly in the chromatogram, we could not detect the delta 5-3 hydroxysteroids such as pregnenolone and dehydroepiandrosterone using the ultraviolet absorption monitor.

Adrenal Cortex Hormones↗