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Biomedical subjects

H Sakamaki

Publications and source records attributed to H Sakamaki.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of additional chromosomal abnormalities in acute promyelocytic leukemia treated with all-trans-retinoic acid: a report of 17 patients.

Seventeen cases of acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and combination chemotherapy at Tokyo Metropolitan Komagome Hospital between 1992 and 1999 were reviewed, and divided into 2 karyotype-based cytogenetic groups. One group comprised 7 patients with either the typical t(15;17) alone or a normal karyotype, and the other group comprised 10 patients with additional karyotypic abnormalities. No patient had received prior chemotherapy or irradiation, and no cases were complicated by a history of myelodysplastic syndrome before the diagnosis of APL. There were no significant differences in clinical characteristics at disease presentation. Complete remission was achieved in all 17 patients and karyotypes of bone marrow cells normalized in all cases. No differences were found in relapse rate, overall survival, or disease-free survival between the 2 groups. The analysis did not reveal any significant effect of additional chromosomal abnormalities on the prognosis of APL patients undergoing treatment with ATRA. However, a small number of patients were assessed in this study, and further cumulative studies are needed.

Adolescent↗
PubMed2001

Hypercalcemia in patients with oral squamous cell carcinoma.

Humoral hypercalcemia of malignancy (HHM) is one of the most common metabolic complications associated with cancer. A retrospective study of hypercalcemia in patients with squamous cell carcinoma of the oral cavity was undertaken. All patients were periodically monitored for their serum level of calcium (Ca). Hypercalcemia was defined as a serum Ca concentration higher than 11 mg/dl of the correction for serum albumin concentration. The serum levels of parathyroid hormone related protein (PTH-rP) were also measured by radioimmunoassay. Hypercalcemia was detected in ten of 246 patients (4.1%). All ten patients were at an advanced stage of oral squamous cell carcinoma (SCC, Stage IVA, IVB or IVC). In these ten patients, the serum level of PTH-rP was significantly elevated, 238 +/- 91 pmol/l (range, 108-380 pmol/L). The patients with HHM who underwent antihypercalcemic therapy showed reduced Ca levels relating to PTH-rP levels; however, the Ca concentration was temporarily improved after anti-hypercalcemic treatment. The median survival time after diagnosis of HHM was only 55.8 +/- 19.9 days (range, 27-86 days). HHM in oral cancer is likely attributable to PTH-rP, and its occurrence appears to be an ominous prognostic sign.

Adult↗
PubMed2001

Biotransformation of thujopsene by Caragana chamlagu.

Biotransformation of thujopsene (1) using a cell suspension culture of Caragana chamlagu for 14 days gave mayurone (2, 52%) and two new compounds, 3beta-hydroxy-4-thujopsene (4, 16%) and 3beta-epoxythujopsa-5beta-ol (3, 22%).

Biotransformation↗
PubMed2001

CTLA4 gene polymorphism contributes to the mode of onset of diabetes with antiglutamic acid decarboxylase antibody in Japanese patients: genetic analysis of diabetic patients with antiglutamic acid decarboxylase antibody.

AIM: The mode of onset is occasionally similar in Type 1 and Type 2 diabetes mellitus, and some patients with Type 2 diabetes are positive for antiglutamic acid decarboxylase antibody (GAD Ab). We investigated the contribution of Type 1 diabetes susceptibility genes to the progression of the insulin-deficient state and mode of onset of Type 2 diabetes in GAD Ab-positive (GAD-Ab+) patients. We examined the variable number of tandem repeats in the promoter region of the insulin gene (INS-VNTR, insulin-dependent diabetes mellitus (IDDM) 2) and cytotoxic T lymphocyte antigen 4 (CTLA4, IDDM12) as representative of Type 1 diabetes susceptibility genes. METHODS: Patients with Type 2 diabetes who were GAD-Ab+ (n = 51) were selected for this study. In INS-VNTR, the class I allele was classified according to length (1S, 25-38 repeat units; 1M, 39-41 repeat units; 1L, 42-44 repeat units) and the exact class I allele length was analysed by specific polymerase chain reaction (PCR) amplifications. Analyses of classes II and III were performed by Southern blot. CTLA4 gene polymorphism (exon 1 position 49, G/A) was analysed by PCR-restriction fragment length polymorphism. RESULTS: The distribution of INS-VNTR was no different between Type 1 diabetes and Type 2 diabetes with GAD Ab. The allele frequencies of CTLA4 gene polymorphism G and A in Type 2 diabetes/GAD-Ab+ were significantly different from those of Type 1 diabetes/GAD-Ab+ (G: 53%, A: 47% vs. G: 84%, A: 16%; P < 0.0001). CONCLUSIONS: Our data showed that GAD-Ab+ Japanese patients presenting with Type 2 diabetes have shifted A allele while patients with abrupt onset have shifted G allele of CTLA4 gene polymorphism. Our results suggest that immunological function and polymorphism of the CTLA4 gene may contribute to the pathogenesis and progression of Type 1 diabetes.

Abatacept↗
PubMed2001

Reappraisal of the clinical significance of CD7 expression in association with cytogenetics in de novo acute myeloid leukaemia.

Debate exists over whether CD7 expression indicates an unfavourable prognosis in de novo acute myeloid leukaemia (AML). Meanwhile, the type of cytogenetics is a strong prognostic factor in AML. We analysed 256 de novo adult AML cases and found that the proportion of CD7+ cases increased stepwise from the cases with favourable cytogenetics to the cases with intermediate and unfavourable cytogenetics (3 out of 69 cases, 51 out of 140 cases and 25 out of 47 cases respectively, P < 0.0001). CD7-positivity adversely affected the survival only in the cases with unfavourable cytogenetics (P < 0.03). We recommend that CD7 expression in AML be interpreted in association with the cytogenetics.

Acute Disease↗
PubMed2001

Activities of plasminogen activator, plasmin and kallikrein in synovial fluid from patients with temporomandibular joint disorders.

To measure the activities of plasminogen activator (PA), plasmin and kallikrein, multiple synovial fluid samples were taken from 32 patients with internal derangement (ID) and osteoarthrosis (OA), and nine asymptomatic volunteers. The enzyme activity in synovial fluid from the temporomandibular joint (TMJ) was quantitated by a fluorogenic substrate assay using an enzyme substrate. In fluid samples from the patient group, PA was detected in 24 (31.5%), plasmin in 20 (26.3%) and kallikrein in 53 (96.4%), while none of these enzymes were found in the synovial fluid samples from the control group. There were positive correlations found among PA, plasmin and kallikrein. These results clearly demonstrated increased levels of PA, plasmin and kallikrein activities in the synovial fluid of patients with ID and OA, and suggest that these enzymes may be involved in the pathogenesis of synovitis, as well as the resorption of cartilage and bone in TMJ.

Adolescent↗
PubMed2001

Primary sclerosing cholangitis complicated with idiopathic thrombocytopenic purpura.

We present a 66-year-old woman with primary sclerosing cholangitis (PSC) complicated with idiopathic thrombocytopenic purpura (ITP). Both PSC and ITP are considered to reflect an immunological disturbance. However, their coexistence is very rare and to the best of our knowledge this is only the second reported case. In Japan, PSC patients are rarely treated with liver transplantation. Fortunately, the present patient underwent successful hepatic transplantation from a brain-dead donor and simultaneous splenectomy. This case emphasizes the importance of liver transplantation as an effective treatment for primary sclerosing cholangitis.

Aged↗
PubMed2001

[Feasibility of early tapering and discontinuation of cyclosporine to intensify the graft-versus-leukemia effect in patients with advanced hematologic neoplasms].

Twenty patients with advanced hematological malignancies at high risk of relapse who had each received a bone marrow transplant from a matched sibling were registered between October 1996 and January 2000. Cyclosporine (CSP) was tapered on day 40 and stopped on day 50 in 10 patients without prior grade II-IV acute graft-versus-host disease (GVHD), relapse or active infection. These patients were eligible for early tapering of CSP. Although grade II/III acute GVHD was observed in three patients and chronic GVHD in eight patients after CSP tapering, no patients died of GVHD. Three patients died due to disease relapse and one patient died of idiopathic interstitial pneumonia while in remission. The probability of event-free survival at 2 years was 60%. These result indicate that early tapering and withdrawal of CSP is feasible and may provide a graft-versus-leukemia effect in patients with advanced leukemia.

Adult↗
PubMed2000

The Japanese multicenter open randomized trial of ursodeoxycholic acid prophylaxis for hepatic veno-occlusive disease after stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a common transplant-related complication of stem cell transplantation. There is no safe and proven therapy for established VOD, and attempts have focused on its prevention. Limited studies have suggested that prophylactic use of ursodeoxycholic acid (UDCA) reduced the incidence of VOD. To confirm the preventive effect of UDCA on VOD, we conducted a prospective, unblinded randomized, multicenter study of UDCA involving 132 patients who underwent stem cell transplantation for a variety of disorders. Sixty-seven patients were assigned to the UDCA-treated group, and 65 patients were assigned to the control group. The clinical characteristics of the two groups were similar with respect to primary diagnosis, age, sex, and baseline organ function. The preparative regimen and GVHD prophylaxis did not differ significantly between the two groups. UDCA was highly effective in preventing VOD, which occurred in only 3.0% in the UDCA-treated group, as opposed to 18.5% in the control group (P = 0.0043). There were no adverse effects attributable to UDCA. The initial promising report of a prophylactic effect of UDCA on VOD after stem cell transplantation was confirmed in this prospective study.

Adult↗
PubMed2000

Mental disturbances during isolation in bone marrow transplant patients with leukemia.

The mental status of 39 leukemia patients, who received bone marrow transplants (BMT), was studied during the period of isolation. Mental disorders (diagnosed according to DSM-IV criteria) occurred in 16 patients (41%) during the observation period. The most frequent diagnoses were adjustment disorders, with anxiety and/or depression. Logistic regression analysis suggested higher Tension-Anxiety score in the Profile of Mood States (POMS) prior to isolation (P = 0.011), donation of the bone marrow from unrelated subjects (P = 0.026) and in female patients (P = 0.033). The results are preliminary, but indicate a high frequency of mental disturbances and highlight the importance of psychiatric intervention in BMT patients. Bone Marrow Transplantation (2000) 25, 315-318.

Adolescent↗
PubMed2000

Shortening of telomeres in recipients of both autologous and allogeneic hematopoietic stem cell transplantation.

Telomere length of peripheral blood mononuclear cells (PBMCs) from 23 autologous HSCT patients ranging from 4 to 61 years old, and 46 allogeneic HSCT recipients from 6 to 52 years old were studied to confirm whether excessive shortening of telomeres is associated with HSCT. After autologous HSCT, telomere length of PBMCs ranged from 6.8 to 12.0 kb. The comparison between transplanted PBMCs and PBMCs after autologous HSCT showed shortening by up to 1.9 kb (mean +/- s.d.: 0.64 +/- 0.50 kb). There was a difference between autologous HSCT patients and normal volunteers in the slopes of regression lines. After allogeneic HSCT, telomere length of PBMCs ranged from 6.8 to 12.0 kb. Telomeres of recipients were up to 2.1 kb (0.60 +/- 0.468 kb) shorter than those of donors. The slope of regression lines for allogeneic HSCT patients and normal volunteers were parallel. Although all patients were transplanted with more than 2.0 x 10(8) cells/kg, telomere length did not correlate with the number of transplanted cells. There was no significant correlation between telomere length and recovery of hematological parameters. However, three patients with an average telomere length of 6.8 kb after HSCT took a longer period to reach the normal hematological state. Taken together, these data suggest that most HSCTs are performed within the biological safety range of telomeres, while the patients who have telomeres shorter than 7.0 kb after HSCT should be observed carefully for long-term hematopoiesis and the occurrence of hematopoietic disorders.

Adolescent↗
PubMed2000

Predictive markers for hepatic veno-occlusive disease after hematopoietic stem cell transplantation in adults: a prospective single center study.

Hepatic veno-occlusive disease (VOD) is a major complication after hematopoietic stem cell transplantation (HSCT). Aetiological determinants, diagnosis and treatment remain unclear. Changes in coagulation-fibrinolysis parameters and N-terminal propeptide for type III procollagen (P-III-P) have been studied in patients with or without VOD after HSCT. We prospectively measured protein C activity, tissue plasminogen activator (t-PA), antithrombin III (AT-III), plasminogen activity (PLG), thrombin-antithrombin III (TAT), alpha2-plasmin inhibitor (alpha2-PI),fibrinogen (Fbg) and P-III-P in 44 consecutive adult patients undergoing allogeneic HSCT. Each parameter was determined before conditioning, on day 0 of HSCT and weekly for 5 weeks. Five of the 44 patients developed VOD at a median post HSCT of day 3 (range, day 3 to 12). On repeated analysis of variance (ANOVA), there were significant differences between patients with and without VOD in P-III-P (P < 0.0001), protein C (P < 0.0001), t-PA (P < 0.0001), PLG (P < 0.0001), AT-III(P < 0.0001), Fbg (P < 0.0001), alpha2-PI (P = 0.0002). Levels of P-III-P were significantly higher in patients with VOD than without VOD, before preparative chemotherapy (P < 0.005) and on days 0 and 7 (P < 0.001). On day 0, levels of t-PA were significantly higher in patients with VOD than without VOD (P < 0.05). On day 7, levels of protein C were significantly lower in patients with VOD than without VOD (P < 0.01). On day 0, there were trends of differences (P = 0.0515) between patients with and without VOD in the levels of protein C. These results suggest P-III-P, t-PA and protein C are predictive markers for VOD after HSCT in adults. Moreover, the serum P-III-P level before start of conditioning might indicate patients at risk for developing VOD.

Adolescent↗
PubMed2000

The effect of granulocyte colony-stimulating factor administration in healthy donors before bone marrow harvesting.

To investigate whether granulocyte colony-stimulating factor (G-CSF) administration to donors before harvest may lighten the burden imposed on them and accelerate the bone marrow (BM) recovery, we administered 2 microgram/kg/d of G-CSF for five consecutive days before the marrow harvest. All of the donors tolerated the G-CSF administration well without severe adverse events. After 5 d of G-CSF treatment, CD34+ cells and granulocyte-macrophage colony-forming units (GM-CFU) in the donors' BM exceeded baseline values by 4.2-fold (range 0.71-316) and 1.6-fold (0.28-118) respectively. The concentration of total nucleated cells (x 107/ml) in the graft increased from 1.61 (0.95-3.23) to 2.44 (1.27-4.01). Although we collected 1020 ml of BM and obtained 1.50 x 1010 nucleated cells from unprimed donors, 940 ml of BM were sufficient to obtain 2.14 x 1010 nucleated cells from primed donors. However, G-CSF-primed BM did not shorten the time to tri-lineage engraftment and the duration of hospitalization compared with unprimed BM, although primed BM contained more CD34+ cells than baseline values. We consider that the advantages of BM priming are not the acceleration of BM recovery but rather the reduction of blood loss during BM harvesting.

Adolescent↗
PubMed2000

Increased insulin sensitivity and decreased insulin secretion in offspring of insulin-sensitive type 2 diabetic patients.

To investigate the early defects of glucose metabolism in insulin-sensitive type 2 diabetes, we performed oral and frequently sampled intravenous glucose tolerance tests (OGTT and FSIGT) with minimal model analysis in 15 offspring of Japanese type 2 diabetics with normal insulin sensitivity (insulin resistance index of homeostasis model assessment [HOMA-R] < 2.0) and in 20 healthy control subjects without a family history of type 2 diabetes. The frequency of impaired glucose tolerance (IGT) was 40% (6 of 15) in the offspring and 0% (0 of 20) in the controls. Fasting plasma glucose (4.8 +/- 0.1 v4.6 +/- 0.1 mmol/L, P = .18) and immunoreactive insulin ([IRI] 29.9 +/- 2.5 v 28.3 +/- 2.5 pmol/L, P = .64) were comparable between the offspring and the controls. The rate of glucose disappearance (KG) was significantly lower in the offspring versus the control group (2.00 +/- 0.22 v 2.60 +/- 0.17 min(-1), P= .03). The insulin sensitivity index (Si) was significantly greater in the offspring versus the controls (2.68 +/- 0.41 v 1.71 +/- 0.17 x 10(-4) min(-1) x pmol/L , P = .02). First-phase insulin secretion (FPI) to intravenous glucose was significantly lower in the offspring versus the control group (886 +/- 110 v 2,296 +/- 267 min x pmol/L, P< .01). Glucose effectiveness (SG) was comparable between the offspring and control groups. The disposition index (Si x FPI) was significantly lower in the offspring versus the controls (2,106 +/- 256 v 3,652 +/- 490 x 10(-4), P = .02). When the offspring were subdivided into 2 groups by glucose tolerance status, both normal glucose tolerance (NGT) offspring and IGT offspring showed a significant decrease in FPI and increase in Si. Thus, although the offspring of insulin-sensitive type 2 diabetics had increased insulin sensitivity, the impairment in insulin secretion was more dominant. Our results suggest that the early metabolic abnormality in insulin-sensitive type 2 diabetes is an insulin secretory dysfunction despite increased insulin sensitivity.

Adult↗
PubMed2000

Serum levels of soluble interleukin-2 receptor after bone marrow transplantation: a true marker of acute graft-versus-host disease.

To examine whether serum levels of soluble interleukin-2 receptor (sIL-2R) may be a good marker of acute graft-versus-host disease (aGVHD), they were determined weekly in 56 patients receiving bone marrow transplantation (BMT). Because of wide variation in the pre-transplant sIL-2R levels (from 135 to 1918 IU/ml), we used a sIL-2R index in this study by comparing the peak levels with the pre-transplant levels. In agreement with previous reports, there was a significant correlation between the grade of aGVHD and the maximal sIL-2R index. The maximal sIL-2R index was 4.66 in patients with grade I to IV aGVHD, whereas it was 2.68 in patients without GVHD. This marker may be useful for monitoring the status of aGVHD. However, it was interesting that sIL-2R levels were elevated from the time of transplantation until the third week even in patients without GVHD or those who received autologous transplantation. Until the third week, no significant differences were observed in sIL-2R index between these patients and those who developed aGVHD during their clinical courses. After the fourth week, a higher sIL-2R index was observed in patients with aGVHD than in the other patients. Some factors other than GVHD contribute to the elevation of serum sIL-2R levels, and we should recognize the limitations of the measurement of this cytokine.

Adolescent↗
PubMed2000

[A retrospective study of the length of hospitalization following allogeneic bone marrow transplantation].

To estimate the length of hospitalization following bone marrow transplantation(BMT), we conducted a retrospective study of 190 patients who had received allogeneic BMTs at our institution. By our criteria, patients were considered ready for discharge if they were afebrile, did not need intravenous chemotherapy or blood transfusions more than 2 times per week, had maintained these conditions for 1 week or more, and also had no medical history of hepatic veno-occlusive disease, grade-II-or-higher graft-versus-host disease, interstitial pneumonitis, or severe hepato-renal dysfunction. The median length of hospitalization was 108.5 days. Of 82 patients who satisfied our discharge criteria by their 70th hospital day, 10 experienced mild complications during the next 30 hospital days. Of 89 patients who were considered ready for discharge by the 40th hospital day, 30 and 38 experienced complications during the next 30 and 60 hospital days, respectively, and 16 required emergency treatment. No significant baseline characteristics distinguished the patients who experienced complications from those who did not, either after 40 or 70 hospital days. This compounded the difficulty of predicting the development of complications in patients who satisfied our discharge criteria. Although management on an outpatient basis should be safe and feasible for BMT patients who meet our discharge criteria by the 70th day of hospitalization, caution is advised for early discharges after only 40 hospital days.

Adolescent↗
PubMed2000

[Varicella-zoster virus infection after hematopoietic stem cell transplantation].

Of 264 patients aged 15 years or more who underwent hematopoietic stem cell transplantation between 1989 and September 1998 at the Tokyo Metropolitan Komagome Hospital, 47 were infected by the varicella-zoster virus (VZV). In 2 patients, visceral disease preceded cutaneous dissemination. One of these patients exhibited gastrointestinal symptoms followed by disseminated skin rash 6 days later. In the other patient, epigastralgia developed and was followed by seizures secondary to meningitis; the appearance of a skin rash 5 days after these initial symptoms yielded the diagnosis. Early diagnosis and treatment of VZV infection are important, especially for patients who present with visceral symptoms suspected to be due to VZV.

Acyclovir↗