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Biomedical subjects

Y Oyama

Publications and source records attributed to Y Oyama.

At least 37 records · Page 2Linked to original sources
PubMed2003

Hematopoietic stem cell transplantation for severe Crohn's disease.

It is clear that some patients with severe Crohn's disease (CD) fail to respond favorably to the standard treatment, including antibody to Tumor Necrosis Factor alpha (TNFalpha), We have embarked on a unique therapy for this group of patients, intense immune suppression followed by autologous hematopoietic stem cell transplantation (HSCT). The response to this approach in our first four patients has been excellent, with there being no significant untoward event from the transplantation and with each patient entering clinical remission in terms of the Crohn's Disease Activity Index off all therapy for CD and no diarrhea or abdominal pain. However, some evidence of minor laboratory abnormalities and slight inflammation of the colon on colonoscopic evaluation persist up to 1 year post-transplant. It is suggested that HSCT should be considered a reasonable option for patients who have failed standard CD therapy, although long-term follow-up will be necessary to confirm the duration of the induced clinical remission.

Abdominal Pain↗
PubMed2003

Allogeneic stem cell transplantation for autoimmune diseases: nonmyeloablative conditioning regimens.

Hematopoietic stem cell transplantation (HSCT) for autoimmune diseases have been, because of safety reasons, overwhelmingly autologous. Results are, in general, encouraging with improvement in quality of life, a remission of up to several years, and perhaps in some diseases improved survival. This indicates that further study of autologous HSCT especially under phase III design is warranted. However, the ultimate goal of HSCT is cure of otherwise incurable autoimmune diseases. For this reason, allogeneic HSCT in carefully selected high-risk patients with autoimmune diseases using strategies to minimize both regimen-related toxicity and graft-versus-host disease (GVHD) is ongoing at Northwestern University and will be reviewed briefly.

Arthritis, Rheumatoid↗
PubMed2003

Ideal or actual body weight to calculate CD34+ cell doses for autologous hematopoietic stem cell transplantation?

The number of CD34+ cells infused influences the speed of hematologic recovery post-transplant. There are limited data on whether ideal (IBW) or actual (ABW) body weight should be used to calculate CD34+ cell dose. We compared the correlation between recovery to 0.5 x 10(9)/l neutrophils and the CD34+ cell dose based upon ABW as well as IBW in 87 patients autografted for cancer. ABW was >or=25% over IBW in 43% of patients. The median number of CD34+ cells administered was 3.6 x 10(6)/kg ABW and 4.2 x 10(6)/kg IBW. The time to neutrophil recovery was 8-15 days (median 10). There was a stronger inverse correlation between CD34+ cell dose/IBW and neutrophil recovery (r(2)=0.308; P<0.0001) than between CD34+ cell dose/ABW and neutrophil recovery (r(2)=0.267; P<0.0001). The median time to neutrophil recovery was comparable for those receiving >or=2 x 10(6)/kg CD34+ cells/kg IBW as well as ABW (10 days) and those receiving >or=2 x 10(6)/kg CD34+ cells/kg IBW but <2/kg ABW (10 days), but was significantly slower for those receiving <2 x 10(6)/kg CD34+ cells/kg IBW (12 days). These data show that the CD34+ cell dose based on IBW is a better predictor of neutrophil recovery after autotransplantation.

Adolescent↗
PubMed2003

Hematopoietic stem cell transplantation for cardiac and peripheral vascular disease.

Recent studies have suggested that marrow and blood hematopoietic stem cells may contribute to nonhematopoietic tissue repair in multiple organ systems. In animal models and more recently in limited human trials, unpurified marrow mononuclear cells and/or subsets of adult hematopoietic stem cells have been reported to contribute to neoangiogenesis. Since the subset of hematopoietic stem cells (HSCs) that are both CD34+ and AC133+ are endothelial cell precursors, clinical trials using autologous AC133+ HSCs isolated with the Miltenyi CLIMACS cell separator and transplanted into patients with ischemic and refractory peripheral vascular or coronary artery disease are being implemented at Northwestern University.

Animals↗
PubMed2002

Cytotoxic effects of methanol, formaldehyde, and formate on dissociated rat thymocytes: a possibility of aspartame toxicity.

Aspartame is a widely used artificial sweetener added to many soft beverages and its usage is increasing in health-conscious societies. Upon ingestion, this artificial sweetener produces methanol as a metabolite. In order to examine the possibility of aspartame toxicity, the effects of methanol and its metabolites (formaldehyde and formate) on dissociated rat thymocytes were studied by flow cytometry. While methanol and formate did not affect cell viability in the physiological pH range, formaldehyde at 1-3 mmol/L started to induce cell death. Further increase in formaldehyde concentration produced a dose-dependent decrease in cell viability. Formaldehyde at 1 mmol/L or more greatly reduced cellular content of glutathione, possibly increasing cell vulnerability to oxidative stress. Furthermore, formaldehyde at 3 mmol/L or more significantly increased intracellular concentration of Ca2+ ([Ca2+]i) in a dose-dependent manner. Threshold concentrations of formaldehyde, a metabolite of methanol, that affected the [Ca2+]i and cellular glutathione content were slightly higher than the blood concentrations of methanol previously reported in subjects administered abuse doses of aspartame. It is suggested that aspartame at abuse doses is harmless to humans.

Animals↗
PubMed2002

Engraftment syndrome: a common cause for rash and fever following autologous hematopoietic stem cell transplantation for multiple sclerosis.

Autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated as a therapy for patients with progressive multiple sclerosis (MS) at risk of debilitating neurological impairment. While preliminary results from a few studies have been reported, little is known about toxicities or outcome of HSCT for MS. We report a relatively frequent triad of non-infectious fever, rash and fatigue or lassitude that may also be associated with pruritus, pulmonary symptoms, and eosinophilia and frequently occurs around engraftment. This syndrome occurred in 26% of our series of patients (5/19) undergoing HSCT for multiple sclerosis. The engraftment syndrome is usually self-limited but may require intervention with systemic corticosteroids.

Adult↗
PubMed2002

Cobe Spectra is superior to Fenwal CS 3000 Plus for collection of hematopoietic stem cells.

One hundred and seventy-seven stem cell apheresis procedures performed on 91 patients using the Fenwal CS 3000 Plus cell separator and 61 procedures performed on 37 patients using the Cobe Spectra cell separator were studied to compare the CD34(+) cell collection efficiencies (CE; the proportion of the total CD34(+) cell content in the blood volumes processed that is harvested) of the two machines. The absolute peripheral blood CD34(+) cell count was comparable for the two groups (P = 0.27). A strong correlation was seen between the blood CD34(+) cell count and the total number of CD34(+) cells collected for the Spectra (r(2) = 0.59; P < 10(-6)) and for the CS 3000 Plus (r(2) = 0.60; P < 10(-6)). No significant correlation emerged between the peripheral blood CD34(+) cell count and the CE of either machine. The total number of CD34(+) cells collected per procedure was comparable (P = 0.51): median 113 x 10(6) for CS 3000 Plus and median 218 x 10(6)for Spectra. CE was significantly higher with the Spectra (median 45.7%, range 9.8-98.6%) than the CS 3000 Plus (median 30.3%, range 1.7-89.3%; P < 0.00001). We conclude that the CD34(+) cell CE of the Spectra is superior to that of the CS 3000 Plus. Therefore, under the usual clinical conditions, Cobe Spectra should be used preferentially for peripheral blood progentor cell collection to maximize the number of hematopoietic stem cells collected.

Blood Cell Count↗
PubMed2002

Reassessing the definition of myeloid engraftment after autotransplantation: it is not necessary to see 0.5 x 10(9)/l neutrophils on 3 consecutive days to define myeloid recovery.

The time to myeloid recovery after autologous hematopoietic stem cell transplantation (HSCT) is usually defined as the first of 3 consecutive days with an absolute neutrophil count (ANC) of >or=0.5 x 10(9)/l (ANC500). Universal documentation of ANC500 for 3 consecutive days, historically required to ensure robust myeloid recovery, has become difficult with a trend towards early discharge and outpatient HSCT. We studied 90 autografted patients to see how frequently ANC declined after having reached >or=0.5 x 10(9)/l. ANC500 was documented on 2 and 3 consecutive days in 14 and 63 patients, respectively. ANC increased by a median of 213% from the 1st to the 2nd day (rise in 75 and unchanged in two), and by a median of 142% from the 2nd day to the 3rd (rise in 60, unchanged in one, and decline in two; higher than the 1st day in the latter three). The increase from the 1st to the 3rd day was 13-3433% (median, 557%). Thus, in all 63 patients, no decline below ANC500 was seen, and the first day with ANC500 was also the first of 3 consecutive days with ANC500. The remaining 13 patients had repeat counts 2-7 days after the 1st day with ANC500 documenting further increase in ANC with no evidence of failed engraftment. These data show that the first day with ANC500 is also consistently the first of 3 consecutive days with ANC500 in autografted patients. Therefore, the traditional definition of myeloid engraftment should be changed to consider the first day with ANC500 as the day of engraftment without necessarily documenting ANC500 on the subsequent 1-2 days. This simple change in definition has significant implications for how data are reported to transplant registries and how peer-review organizations such as the Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT) define completeness of data.

Adolescent↗
PubMed2002

Cellular component of vascular calcification. Fibroblasts are essential for calcium deposition in cultured cells.

It has been reported that calcium deposition and calcium content in cultured human aortic smooth muscle cells (SMC) increased when the cells are incubated in a medium with a high phosphate concentration (2 mM). To determine the cellular components or soluble factors contributing to the deposition, we cultured commercially available SMC, fibroblasts (Fb) and endothelial cells (Ed). These cells and their mixtures were incubated for 10 days in normal or high-phosphate media. Calcium crystals were stained by the von-Kossa staining and counted in the defined area. Calcium content was measured by a colorimetric assay. SMC were incubated in high-phosphate media (up to 2 mM) or beta-glycerophosphate (beta-GP) media, resulting in no obvious deposition of calcium crystals, irrespective of the coating of type I collagen on the dish. Next, various combinations of cells were cultured, and a significant number of depositions were observed only when Fb were included in the combination. The calcium content was significantly higher in cultures of SMC and Fb. The calcium deposition on single or mixture of the cells did not increase compared with control when cells were incubated in a high concentration of phosphate, cultured in the existence of beta-GP or uremic serum. We therefore conclude that Fb, rather than SMC or Ed, are essential for calcium deposition and calcium accumulation in culture. Phosphate concentration in the medium and uremic serum did not influence the deposition of calcium.

Calcification, Physiologic↗
PubMed2001

Solar 8B and hep neutrino measurements from 1258 days of Super-Kamiokande data.

Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0-20.0 MeV. The measured solar neutrino flux is 2.32+/-0.03(stat)+0.08-0.07(syst)x10(6) cm(-2) x s(-1), which is 45.1+/-0.5(stat)+1.6-1.4(syst)% of that predicted by the BP2000 SSM. The day vs night flux asymmetry (Phi(n)-Phi(d))/Phi(average) is 0.033+/-0.022(stat)+0.013-0.012(syst). The recoil electron energy spectrum is consistent with no spectral distortion. For the hep neutrino flux, we set a 90% C.L. upper limit of 40x10(3) cm(-2) x s(-1), which is 4.3 times the BP2000 SSM prediction.

Journal Article↗
PubMed2001

Constraints on neutrino oscillations using 1258 days of Super-Kamiokande solar neutrino data.

We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.

Journal Article↗
PubMed2001

Homeobox protein Hex induces SMemb/nonmuscle myosin heavy chain-B gene expression through the cAMP-responsive element.

Recent studies have shown that the homeobox gene Hex plays an important role in inducing differentiation of vascular endothelial cells. In this study, we examined the expression of Hex in vascular smooth muscle cells (VSMCs) in vitro and in vivo. Immunohistochemistry showed a marked induction of Hex protein in neointimal VSMCs after balloon injury in rat aorta. Western and reverse transcriptase-polymerase chain reaction analyses demonstrated that Hex was abundantly expressed in cultured VSMCs, whereas it was undetectable in other cell types or in normal aorta. The expression pattern of Hex was similar to that of SMemb/NMHC-B, a nonmuscle isoform of myosin heavy chain that we have previously reported to be a molecular marker of dedifferentiated VSMCs. We next examined the role of Hex in SMemb gene transcription. Promoter analysis demonstrated that the sequence identical to consensus cAMP-responsive element (CRE) located at -481 of the SMemb promoter was critical for Hex responsiveness. Mutant Hex expression vector, which lacks the homeodomain, failed to stimulate SMemb gene transcription, suggesting the requirement of the homeodomain for its transactivation. Elecrophoretic mobility shift assay showed that Hex binds to a consensus binding sequence for homeobox proteins, but not to CRE. Cotransfection of protein kinase A expression vector increased the ability of Hex to stimulate SMemb promoter activity in a CRE-dependent manner. Overexpression of CRE binding protein (CREB), but not Mut-CREB which contains mutation at Ser133, strongly activated Hex-induced SMemb promoter activity. These results suggest that Hex mediates transcriptional induction of the SMemb/NMHC-B gene via its homeodomain, and Hex can function as a transcriptional modulator of CRE-dependent transcription in VSMCs.

3T3 Cells↗
PubMed2001

CD34(+) cell collection efficiency does not correlate with the pre-leukapheresis hematocrit.

One hundred and seventy-seven large-volume leukapheresis procedures performed on 91 patients over a 15 month period were reviewed to see if the pre-apheresis hematocrit (Hct) affected the CD34(+) cell collection efficiency (CE) of the Fenwal CS 3000 Plus cell separator. The Hct was 0.174-0.461 (median 0.317), and the peripheral blood CD34(+) cell count 2-2487 per microl (median 21). The total CD34(+) cell quantity collected was 3.0-2677.2 x 10(6) (median 113.0). Based on the number of CD34(+)cells contained in the blood volume processed (23.3-37303.2 x 10(6); median 318.0), the CE was 1.7-87.5% (median 30.3). No correlation was found between the Hct and CE (r(2) = 0.0034; P = 0.44) or the total CD34(+) cell quantity collected (r2 = 0.0040; P = 0.40). CEs for Hct <0.25 (median CE 36%), Hct 0.25-0.299 (median CE 30%) and Hct 0.30 (median CE 30%) were comparable. As expected, highly significant correlations were seen between the CD34(+) cell quantities collected and quantities processed (r2 = 0.59; P < 10(-6)) as well as the peripheral blood CD34(+) cell counts (r2= 0.60; P < 10(-6)). We conclude that the minimum acceptable Hct or hemoglobin level for leukapheresis should be dictated by clinical circumstances because it does not affect stem cell collection.

Antigens, CD34↗
PubMed2001

Allogeneic stem cell transplantation for Evans syndrome.

Evans syndrome is a rare disorder characterized by combined autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Standard treatments consist of transfusions, corticosteroids, splenectomy, IVIG, anabolic steroids, vincristine, alkylating agents, or cyclosporine. In a patient with refractory disease, an allogeneic hematopoietic stem cell transplant (HSCT) resulted in complete clinical and serologic remission for more than 30 months. Allogeneic HSCT may be the only current curative therapy for Evans syndrome but may also be complicated by significant toxicities.

Adrenal Cortex Hormones↗
PubMed2001

Isolation and antioxidant activity of galloyl flavonol glycosides from the seashore plant, Pemphis acidula.

Four kinds of galloyl flavonol glycosides were found in the leaf extract of Pemphis acidula, a plant growing on the subtropical seashore. Their chemical structures were elucidated to be quercetin or kaempferol 6"-O-galloyl-beta-D-glycosides by using spectroscopic and chemical analyses. One of the flavonols, kaempferol-3-O-(6-O-galloyl-beta-D-galactopyranoside), was newly isolated from natural sources and its structure was completely determined in this investigation. The antioxidant-related activities of the galloyl flavonoids were examined by the DPPH antiradical activity, inhibition of methyl linoleate oxidation, and inhibition of oxidative cell death. These results were compared with those of the corresponding non-galloylated flavonol glycosides and their aglycones. The galloyl flavonoids showed more efficient activity than that of the corresponding flavonol glycosides, but not more than that of the corresponding aglycones in the three assays applied.

Africa↗
PubMed2001

Nanomolar concentrations of tri-n-butyltin facilitate gamma-aminobutyric acidergic synaptic transmission in rat hypothalamic neurons.

Tri-n-butyltin (TBT), an environmental pollutant, is accumulated in edible mollusks and fishes. It has also become a health concern in today's society. In the present study, to elucidate the possible neurotoxic action of TBT, the effect on spontaneous gamma-aminobutyric acid (GABA) release from GABAergic nerve terminals projecting to rat ventromedial hypothalamic neurons was examined using "synaptic bouton" preparation with a nystatin perforated patch recording mode under voltage-clamp conditions. The threshold concentration of TBT to affect the synaptic transmission was 10 to 30 nM. TBT at 30 nM or higher concentrations increased the frequency of GABAergic miniature inhibitory postsynaptic currents in a dose-dependent manner, whereas the current amplitude and current kinetics were not affected. The removal of either external Ca2+ or application of Cd2+ attenuated the TBT-induced facilitation of neurotransmission. TBT at 1 microM induced an inward current in more than one-half of the cells. This current persisted even after TBT was washed out. The present results indicate that TBT at environmentally relevant concentrations (30-100 nM) facilitates the GABAergic neurotransmission in the mammalian brain and the external Ca2+ is needed in this facilitation. Because the concentration of TBT accumulated in some mollusks and fishes has been reported to reach levels of 100 nM or more, such accumulation of TBT in some mollusks and fishes is thus suggested to be hazardous to the health of humans.

Animals↗
PubMed2001

Treatment of relapse after autologous blood stem cell transplantation for severe rheumatoid arthritis.

There is little information about the clinical course of patients with rheumatoid arthritis (RA) who relapse after autologous blood stem cell transplantation (ASCT). We describe 6 patients with severe RA who received ASCT in 3 US centers. Duration of followup was between 24 and 42 months posttransplant. Five patients achieved major responses but relapsed 3-22 months posttransplant. Two patients with relapse improved remarkably after restarting disease modifying antirheumatic drugs (DMARD). Two patients developed a mild RA flare at 3 and 5 months posttransplant and improved spontaneously. All 4 patients who improved after an initial disease flare remained highly functional at 14-22 months posttransplant. All patients in this study were anti-tumor necrosis factor (TNF) drug naive; all received a TNF blocker as a second line posttransplant salvage therapy, but only 3 responded. Future ASCT strategies need to focus on improving the durability of the early posttransplant responses.

Adult↗