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Biomedical subjects

K Oshima

Publications and source records attributed to K Oshima.

At least 19 recordsLinked to original sources
PubMed2006

A high incidence of late-onset neutropenia following rituximab-containing chemotherapy as a primary treatment of CD20-positive B-cell lymphoma: a single-institution study.

BACKGROUND: Late-onset neutropenia (LON) has been reported following rituximab-containing chemotherapy. Its incidence and risk factors, however, have not been extensively studied. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 107 patients treated with rituximab-containing chemotherapy as a primary treatment of CD20-positive B-cell lymphomas and identified cases with LON as defined by the neutrophil count of <or=1.0 x 10(9)/l without an apparent cause after the recovery of neutrophil count following completion of the intended chemotherapy. RESULTS: With a median follow-up of 411 days, 23 patients developed LON out of the 107 at a median of 106 days after the last chemotherapy. Cumulative incidence of LON among the total patients was 24.9%. The median neutrophil count nadir was 0.61 x 10(9)/l. The LON episodes were generally self-limited, and filgrastim was administered in one patient. Including this patient, there were no serious infectious episodes in the cases with LON. In multivariate analysis, intensive chemotherapy regimens including high-dose therapy followed by autologous hematopoietic stem cell transplantation (ASCT) and high-dose methotrexate-containing regimens without ASCT were a risk factor for LON. CONCLUSION: This study suggests that LON is a frequent complication of rituximab-containing intensive chemotherapy.

Adult↗
PubMed2006

Preservation of ovarian function by ovarian shielding when undergoing total body irradiation for hematopoietic stem cell transplantation: a report of two successful cases.

The purpose of this study was to evaluate the possibility of preserving ovarian function by ovarian shielding to reduce the irradiation dose in total body irradiation (TBI). The subjects in the study were females aged less than 40 years, who were undergoing allogeneic hematopoietic stem cell transplantation using a TBI-based regimen and who desired to have children after transplantation. For ovarian shielding, abdominal computed tomography (CT) and skin marking were performed in both the supine and prone positions, prior to the TBI. A pair of columnar blocks was placed just above the patient's body. Thus far three patients have been treated. The serum estradiol level decreased to an undetectable level (<8.5 pg/ml) after transplantation and the follicle-stimulating hormone (FSH) level increased above 90 mIU/ml in all patients and they became amenorrheic. However, regular menstruation recovered in patients no. 1 and 2 about 800 and 370 days after transplantation, respectively, with a decrease in the serum FSH level. Menstruation did not recover in patient no. 3, and serum estradiol was transiently detected above 20 pg/ml. The preservation of ovarian function was made possible by ovarian shielding. However, a longer follow-up is needed to know if normal pregnancy and delivery can occur.

Adult↗
PubMed2005

High-grade cytomegalovirus antigenemia after hematopoietic stem cell transplantation.

Clinical impact of high-grade (HG) cytomegalovirus (CMV) antigenemia after hematopoietic stem cell transplantation has not been clarified. Therefore, in order to investigate the risk factors and outcome for HG-CMV antigenemia, we retrospectively analyzed the records of 154 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2002 at the University of Tokyo Hospital. Among 107 patients who developed positive CMV antigenemia at any level, 74 received risk-adapted preemptive therapy with ganciclovir (GCV), and 17 of these developed HG-antigenemia defined as > or = 50 positive cells per two slides. The use of systemic corticosteroids at > or = 0.5 mg/kg/day at the initiation of GCV was identified as an independent significant risk factor for HG-antigenemia. Seven of the 17 HG-antigenemia patients developed CMV disease, with a cumulative incidence of 49.5%, which was significantly higher than that in the low-grade antigenemia patients (4%, P<0.001). However, overall survival was almost equivalent in the two groups. In conclusion, the development of HG-antigenemia appeared to depend on the profound immune suppression of the recipient. Although CMV disease frequently developed in HG-antigenemia patients, antiviral therapy could prevent a fatal outcome.

Adolescent↗
PubMed2005

Cardiac complications after haploidentical HLA-mismatched hematopoietic stem cell transplantation using in vivo alemtuzumab.

Alemtuzumab is a humanized monoclonal antibody directed against human CD52 with a strong lympholytic effect. We have performed unmanipulated hematopoietic stem cell transplantation (HSCT) from 2- or 3-locus-mismatched family donors in 14 patients using in vivo alemtuzumab. All achieved complete donor cell engraftment and grade III-IV acute graft-versus-host disease was observed in only one patient. However, eight of the 14 patients developed grade II-IV cardiac complications according to Bearman's criteria. Next, we retrospectively analyzed the records of 142 adult patients who underwent allogeneic HSCT from 1995 to 2004 to evaluate whether the use of alemtuzumab was an independent risk factor for cardiac complications. Among several factors that increased the incidence of grade II-IV cardiac complications with at least borderline significance, a multivariate analysis identified the cumulative dose of anthracyclines (P=0.0016) and the use of alemtuzumab (P=0.0001) as independent significant risk factors. All of the cardiac complications in the alemtuzumab group were successfully treated with diuretics and/or catecholamines. Patient selection and close monitoring of cardiac function may be important in HLA-mismatched HSCT using in vivo alemtuzumab.

Adult↗
PubMed2005

Impairment of thrombospondin-1 expression during epithelial wound healing in corneas of vitamin A-deficient mice.

The purpose of this study is to investigate the expression of thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein, during re-epithelialization in wounded corneas of vitamin A-deficient mice. Epithelial defects were created in the corneas of normal and Vitamin A-deficient mice with a microgrinder. Wounded corneas were stained with fluorescein and photographed for evaluation of re-epithelialization. Histological examination and immunohistochemical analysis of TSP-1 expression were also performed on the specimens from wounded corneas. In vitamin A-deficient mice, re-epithelialization of the wounded corneal epithelium was significantly delayed compared with that in normal mice. TSP-1 was detectable neither in the unwounded corneal epithelium of normal mice nor in that of vitamin A-deficient mice. In normal mice, linear staining of TSP-1 was observed on the wounded corneal surface and stroma at 30 min and 8 h to 16 h, respectively, after abrasion, and this TSP-1 expression disappeared at 36 to 48 h, when re-epithelialization was completed. In contrast, no TSP-1 staining was observed in the wounded corneas of vitamin A-deficient mice, except for the endothelial cells, throughout the wound healing process. Histological examination revealed a progressive increase in polymorphonuclear neutrophil infiltration in the stroma of the corneas of vitamin A-deficient mice during the healing process. These findings suggest that vitamin A may modulate the expression of TSP-1 in the corneas to accelerate the re-epithelialization of wounded corneas.

Animals↗
PubMed2004

Treatment with buserelin, an agonist of gonadotropin-releasing hormone, suppresses ovarian hyperstimulation syndrome induced in rabbits.

Human menopausal gonadotropin (hMG, 75 IU/body/day) and a gonadotropin-releasing hormone (GnRH) agonist buserelin (1, 10, 100 microg/kg/day) were simultaneously administered to female rabbits by the subcutaneous route for 7 days, and the effects on organ weights, plasma hormones and weight of ascitic fluid were examined. Treatment with hMG increased the ovarian weight, plasma estradiol and weight of ascites, thus indicating that ovarian hyperstimulation syndrome had been induced. Simultaneous treatment with buserelin decreased the changes induced by hMG. GnRH agonists can thus be surmised to reduce the severity of ovarian hyperstimulation syndrome in the rabbit. However, caution is needed when extrapolating the results of this rabbit model to humans.

Animals↗
PubMed2003

Gene expression of leukemia inhibitory factor (LIF) and macrophage colony stimulating factor (M-CSF) in bovine endometrium during early pregnancy.

Leukemia inhibitory factor (LIF) and macrophage colony stimulating factor (M-CSF), members of the group of hemopoietic cytokines, play a primary role in the control of embryo development and implantation and in the growth of the placenta in humans and mice. Gene expressions of LIF and M-CSF were investigated using quantitative RT-PCR in bovine endometrial tissues during early and mid-pregnancy (Days 16-17, 20-21, 30-36, 48-49 and 74-140) and during the estrous cycle (Days 13-14). Leukemia inhibitory factor and M-CSF genes were expressed in all samples examined. Significant differences were found between the gene expression patterns of LIF and M-CSF. Leukemia inhibitory factor expression level at Days 48-49 was the highest in caruncular endometrium, however, the large variability negated any significant differences. Leukemia inhibitory factor expression levels in intercaruncular endometrium at Days 48-49 and 74-140 of pregnancy were greater than at Days 13-14 of the estrous cycle and at other days of pregnancy. No significant change was recognized in M-CSF expression levels in caruncular endometrium. Macrophage colony stimulating factor expression level in intercaruncular endometrium at Days 74-140 was greater than those of the other samples. These results suggest that LIF and M-CSF are produced in the endometrium and may play different roles in early and mid-pregnancy.

Animals↗
PubMed2003

Quantitation of bovine macrophage colony-stimulating factor in bovine serum by ELISA.

We established an enzyme-linked immunosorbent assay (ELISA) system for the quantitation of bovine macrophage colony-stimulating factor (M-CSF) and used it to measure the serum M-CSF levels in bovine fetuses and calves. The average serum M-CSF level was 2.7+/-1.5 ng/ml in 39 calves under 100 days old, and 1.8+/-0.8 ng/ml in 15 cattle between 101 and 418 days old. Fetal sera samples (n = 6) prepared from cattle between 150 and 280 days of gestational age had a higher average level of M-CSF (8.8+/-1.4 ng/ml). Alteration in serum M-CSF levels in each individual calf was also measured. The serum levels of M-CSF in calves at 0-1 day after birth ranged from 0.52 to 7.3 ng/ml. During the period 113-125 days after birth, serum levels were around 1.4+/-0.39 ng/ml. Although serum M-CSF levels generally decreased as the age of calves advanced, differences among individuals, especially among newborn calves, were observed.

Age Factors↗
PubMed2003

Anti-metastatic and anti-angiogenic activities of a new matrix metalloproteinase inhibitor, TN-6b.

We investigated the anti-metastatic and anti-angiogenic effects of TN-6b, a new broad-spectrum inhibitor of matrix metalloproteinases (MMPs), against Lewis lung carcinoma (LLC) and hepatic sinusoidal endothelial (HSE) cells. TN-6b potently inhibited the activities of MMP-2 and -9 secreted by LLC and HSE cells in a zymogram assay. TN-6b, at non-cytotoxic concentrations, caused a marked inhibition of invasion and migration of LLC, and tube-like formation of HSE cells. In contrast, TN-6d, an inactive enantiomer of TN-6b, did not inhibit the invasion and tube-like formation. Daily subcutaneous (s.c.) administration of TN-6b at doses of 30 and 60 mg/kg in mice resulted in a potent inhibition of tumour-induced angiogenesis of B16 melanomas and lymph node metastasis of LLC cells. In conclusion, TN-6b effectively inhibited lymph node metastasis of LLC cells through its anti-invasive and anti-angiogenic properties. These findings suggest that the MMP inhibition correlates well with its anti-angiogenic and anti-metastatic efficacy and TN-6b has the therapeutic potential to inhibit angiogenesis and metastasis in vivo and in vitro.

Angiogenesis Inhibitors↗
PubMed2003

Acute effects of ethanol on feeding behavior and leptin-induced STAT3 phosphorylation in rat hypothalamus.

OBJECTIVE: Drinking ethanol stimulates the appetite, producing a positive energy balance. The mechanism by which ethanol regulates the appetite in the central nervous system, however, has not been fully understood. The aim of this study is to investigate the interaction of ethanol with the satiety effect of leptin, a hormone which suppresses the appetite in the hypothalamic region. DESIGN: : Leptin (7.5 micro g) or the same dose of phosphate buffer saline (PBS) was administered into the third ventricle (i.c.v.), 30 min after an intraperitoneal injection (i.p.) of ethanol (0.5 g/kg body weight) or the same dose of PBS. MATERIALS: Adult male Sprague-Dawley rats weighing 290-320 g were used. MEASUREMENTS: Food intake was measured 2, 12 and 24 h after leptin i.c.v. infusion. The tyrosine phosphorylation of signal transducer and activator transcription factor 3 (STAT3) in the hypothalamus was analyzed by Western blotting. RESULTS: The cumulative food intakes in the saline/leptin group (saline i.p.+leptin i.c.v.) were markedly reduced to about 45% of the saline/PBS group (saline i.p.+PBS i.c.v.) at 2, 12 and 24 h time points (P<0.05, 0.001, and 0.005, respectively). As compared with the saline/leptin group, those of the ethanol/leptin group (ethanol i.p.+leptin i.c.v.) were significantly increased to the level seen in the saline/PBS group at 12 and 24 h time points (P<0.05, and P<0.005 vs the saline/leptin group, respectively). Ethanol administration resulted in about a 50% reduction of the leptin-induced STAT3 tyrosine phosphorylation seen in the hypothalamic protein as compared to that of the saline/leptin group. CONCLUSION: These findings suggest that ethanol-induced enhancement of the appetite may, in part, result from leptin resistance transiently caused by ethanol to attenuate the leptin signal transduction.

Animals↗
PubMed2003

Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity.

AIMS: To search for mutations in the frizzled 4 (FZD4) gene in patients with familial exudative vitreoretinopathy (FEVR) and to delineate the defective gene associated clinical features. METHODS: Direct sequencing following polymerase chain reaction of exons of FZD4 was performed for 24 probands with FEVR (18 familial and six sporadic), and some of their families. Clinical symptoms among individuals with mutations were assessed. RESULTS: Four novel mutations were identified in four patients with familial and one with sporadic FEVR. Three of these mutations were missense (M105V, R417Q, and G488D) and one was a nonsense change (W319X). M105V, R417Q, and G488D co-segregated with the disease. None of these sequence changes was found among 300 chromosomes from 150 healthy volunteers. The severity of vitreoretinopathy in the individuals involved in this study varied, but no patient with mutations in FZD4 exhibited rhegmatogenous retinal detachment although this pathology is thought to be the most common type of retinal detachment in FEVR. CONCLUSION: FZD4 gene mutations were found in some cases of autosomal dominant and sporadic FEVR. FZD4 mutations were responsible for FEVR with variable clinical manifestations.

Adolescent↗
PubMed2002

The diagnostic value of kappa/lambda ratios determined by flow cytometric analysis of biopsy specimens in B-cell lymphoma.

Flow cytometry (FC) is widely utilized in the diagnosis of lymphoma and the light chain ratio (LCR) is especially useful in the diagnosis of B-cell malignancy. In this study we analysed, retrospectively, the predictive value of the LCR in the diagnosis of B-cell lymphoma in 105 consecutive patients with persistent lymph node enlargement or extranodal masses who underwent biopsy. We used a receiver-operating characteristic curve to establish a LCR threshold value of 2.0. The specificity, sensitivity, positive and negative predictive values were 92.3%, 73.1%, 90% and 77%, respectively. We concluded that determination of LCR is a useful adjunct to pathological diagnosis.

Adolescent↗
PubMed2002

Analyses of serum lipoprotein(a) and the relation to phenotypes and genotypes of apolipoprotein(a) in type 2 diabetic patients with retinopathy.

To elucidate the association of lipoprotein(a) (Lp(a)) with diabetic retinopathy (DR), we studied the serum Lp(a) concentrations (n = 412), apolipoprotein(a) (apo(a)) phenotypes expressed by the number of kringle 4 (K4) repeats (n = 150), apo(a) gene genotypes (n = 161) of type 2 diabetes with or without DR. The 5'-untranslated region of apo(a) gene was classified into seven haplotypes (A to G) and 18 genotypes by PCR-RFLP at three distinct sites. The serum Lp(a) concentrations were significantly higher in diabetic patients than in normal controls. Furthermore, the patients with DR, especially proliferative retinopathy showed higher serum Lp(a) concentrations than those without DR. Although a negative correlation was found between the serum Lp(a) concentrations and the number of K4 repeats in total diabetic patients, no difference was seen in the distribution of the number of K4 repeats between those with and without DR. In the same apo(a) phenotypes, the patients with DR had higher Lp(a) concentrations than those without DR. Among the genotypes, type CC showed significantly higher serum Lp(a) concentrations than the other genotypes. However, there was no difference in the ratios of the type CC between the patients with and without DR. In conclusion, other factors than phenotypes and genotypes in the 5'-untranslated region of apo(a) may be responsible for the elevation of serum Lp(a) in diabetic patients with retinopathy.

5' Untranslated Regions↗
PubMed2002

STAT and SMAD signaling in cancer.

STAT and SMAD often exert opposite biological effects on diverse cellular functions. Recent studies have shown that STAT can interface with SMAD at molecular level and that some novel molecules, such as SOCS (also called CIS) and APRO6 (also called TOB), modulate this signaling. A cofactor p300/CBP might act as a bridging molecule to mediate the interface. Thus, STAT and SMAD signaling pathways may crosstalk each other with interweaved regulatory mechanisms. Interestingly, the importance of all the proteins' function has been shown by the increasing evidence of their involvement in cancer. These recent progresses have been made in attributing novel exciting functions. Accordingly, we would like to review the latest advances of those pathways on a cross-section in cancer signaling.

Animals↗
PubMed2002

Lung impairment following cardiac surgery in patients with pulmonary hypertension.

BACKGROUND: Postoperative respiratory management following cardiac surgery is sometimes troublesome in patients with pulmonary hypertension. We retrospectively studied the relationship between the etiology of preoperative pulmonary hypertension and the postoperative decline of blood oxygenation capacity by focusing on the postoperative intravascular fluid volume. METHODS: Sixteen adult patients with an atrial septal defect (preload group) and 17 patients with solitary mitral valve disease (afterload group) were studied. The mean age of the patients in the preload and afterload group was 51 and 52 years old, respectively. RESULTS: Preoperative pulmonary-systemic pressure ratio and pulmonary artery resistance index were significantly higher in the preload group than in the afterload group. The respiratory index (RI) and the pulmonary shunt ratio (Qs/Qt) measured immediately after the operation was larger in the afterload group than in the preload group. Postoperative RI and Qs/Qt remained high until postoperative day 3 in both groups. In the preload group RI on postoperative day 1 had a reverse correlation with the central venous pressure (CVP). Meanwhile, the RI in the afterload group on postoperative day 1 was slightly larger in patients with a high CVP and pulmonary capillary wedged pressure. Similar relationships were seen in the relations between pulmonary capillary wedged pressure and RI in the afterload group. CONCLUSIONS In conclusion, a preoperative pulmonary vascular change and a postoperative precipitous decrease of pulmonary blood flow may have caused postoperative lung oxygenation impairment in the preload group. An extended period of extracorporeal circulation associated with cardiac arrest and postoperative volume overload may have caused lung impairment in the afterload group. In aspect of postoperative management, low CVP is beneficial to the patients in the afterload group, however, hypovolemia should be avoided in patients of the preload group.

Blood Gas Analysis↗
PubMed2002

Peripheral pulmonary atelectasis and oxygentation impairment following coronary artery bypass grafting.

BACKGROUND: Severe pulmonary oxygenation impairment occurred in some patients with pleurotomy during the harvest of the internal mammary artery graft followed by coronary artery bypass grafting (CABG). Peripheral pulmonary atelectasis in the postoperative chest X-ray was detected in these patients. We studied the efficacy of intraoperative positive end-expiratory airway pressure (PEEP) therapy for the prevention of postoperative pulmonary oxygenation impairment. METHODS: The pleural cavity was intraoperatively opened in 40 patients with solitary CABG procedure performed during 5 years since January 1992. These patients were divided into two groups. Intraoperative PEEP therapy, which is initiated just after pleurotomy, was not used in 32 patients before May, 1996 (control group) and used for recent 8 patients with pleurotomy (PEEP group). The mean age of patients was 60 years old in the control group and 68 in the PEEP group. RESULTS: Respiratory insufficiency (A-aDO2 >400 mmHg and RI >1.5) was detected in 6 patients in the control group. Three out of these 6 patients required long-term mechanical respiratory support over a week. No respiratory insufficiency occurred in patients of the PEEP group. Values of PaO2, A-aDO2, respiratory index and shunt ratio were significantly worse in the control group than in the PEEP group. CONCLUSIONS: In conclusion, PEEP therapy may prevent pulmonary atelectasis and oxygen impairment after CABG.

Aged↗