Biomedical subjects

K Kogure

Publications and source records attributed to K Kogure.

At least 127 records · Page 7Linked to original sources

PubMed1994

Induction of 27-kDa heat shock protein following cerebral ischemia in a rat model of ischemic tolerance.

Preconditioning the brain with sublethal cerebral ischemia induces tolerance to subsequent lethal periods of ischemia (ischemic tolerance). The purpose of this study is to investigate the role of low-molecular weight stress proteins, 27-kDa heat shock protein (HSP27) and alpha B crystallin, in ischemic tolerance. We measured the content of these proteins with enzyme immunoassay in the rat hippocampus and cerebral cortex following 6 min of ischemia with and without preconditioning with 3 min of ischemia and 3 days of reperfusion. We also visualized the localization of HSP27 immunohistochemically in comparison with that of HSP70. A 3-min period of ischemia caused a 2.4-fold increase in HSP27 content in the hippocampus after 3 days. Immunohistochemical localization of HSP27 was found in glial cells in all subregions of the hippocampus, whereas HSP70 immunostaining was seen only in CA1 pyramidal neurons. HSP27 content in the hippocampus decreased 2 h after 6 min of ischemia. HSP27 content progressively increased in the unpreconditioned hippocampus after 1 and 3 days, but returned to preischemic levels in the preconditioned hippocampus. HSP27 and HSP70 immunostaining was seen in CA1 pyramidal neurons after 1 day both with and without preconditioning. After 3 and 7 days, an intense HSP27 staining was observed in reactive glial cells in the CA1 without preconditioning, whereas the staining decreased in the preconditioned hippocampus. HSP70 staining was seen only in neurons at these time points. We observed no significant changes in HSP27 content in the cerebral cortex although neurons in the third and fifth layers were immunostained after 1 and 3 days. We observed no alterations in alpha B crystallin content after ischemia both in the hippocampus and the cortex. The present study demonstrated that cerebral ischemia induces HSP27 expression but not alpha B crystallin. Both HSP27 and HSP70 induction had a good temporal correlation with the induction of ischemic tolerance. However, different sites of action were suggested because the localization and cell types of HSP27 induction were quite different from those of HSP70 induction. The result suggests that it is unlikely that HSP27 is directly involved in the protection afforded by ischemic preconditioning.

Adaptation, Physiological↗

PubMed1994

Blocking of interleukin-1 activity is a beneficial approach to ischemia brain edema formation.

We examined the therapeutic value of an interleukin-1 inhibitor on brain edema formation using a transient focal ischemia model in rats. Rats were given an interleukin-1 blocker, or interleukin-1 release inhibitor immediately after reperfusion. In rats treated with interleukin-1 inhibitor, ischemic brain edema 1 day after reperfusion was significantly decreased compared to that of saline-treated control rats. The simultaneous application of an IL-1 release inhibitor and a lipoxygenase inhibitor showed an additive beneficial effect on brain edema formation. These findings suggest that blocking IL-1 activity ameliorates brain edema and attenuates the neuronal damage induced by focal transient ischemia in rats.

Animals↗

PubMed1994

Age-dependent changes in second messenger and rolipram receptor systems in the gerbil brain.

Age-related alterations in binding sites of major second messengers and a selective adenosine 3',5'-cyclic monophosphate (cyclic-AMP) phosphodiesterase (PDE) in the gerbil brain were analysed by receptor autoradiography. [3H]Phorbol 12,13-dibutyrate (PDBu), [3H]inositol 1,4,5-trisphosphate (IP3), [3H]forskolin, [3H]cyclic-AMP, and [3H]rolipram were used to label protein kinase C (PKC), IP3 receptor, adenylate cyclase, cyclic-AMP dependent protein kinase (PKA), and Ca2+/calmodulin-independent cyclic-AMP PDE, respectively. In middle-aged gerbils (16 months old), [3H]PDBu binding was significantly reduced in the hippocampal CA1 sector, thalamus, substantia nigra, and cerebellum, compared with young animals (1 month old). [3H]IP3 binding revealed significant elevations in the nucleus accumbens, hippocampal CA1 sector, dentate gyrus, and a significant reduction in cerebellum of middle-aged gerbils. [3H]Forskolin binding in middle-aged animals was significantly increased in the nucleus accumbens and hilus of dentate gyrus, but was diminished in the substantia nigra and cerebellum. On the other hand, in middle-aged animals, [3H]cyclic-AMP binding revealed a significant elevation only in the hippocampal CA3 sector, whereas [3H]rolipram binding showed a significant reduction in the thalamus and cerebellum. Thus, the age-related alteration in these binding sites showed different patterns among various brain regions in middle-aged gerbils indicating that the binding sites of PKC, IP3, and adenylate cyclase are more markedly affected by aging than those of PKA and cyclic-AMP PDE and that the hippocampus and cerebellum are more susceptible to these aging processes than other brain regions. The findings suggest that intracellular signal transduction is affected at an early stage of senescence and this may lead to neurological deficits.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1994

An immunohistochemical study of parvalbumin containing interneurons in the gerbil hippocampus after cerebral ischemia.

We investigated postischemic changes of non-pyramidal neurons in the gerbil hippocampus 1 h - 7 days after 10 min of cerebral ischemia, with parvalbumin and microtubule-associated protein 2 (MAP2)-immunohistochemistry. Parvalbumin-immunoreactive interneurons in the hippocampus were unaffected up to 24 h after ischemia. A slight reduction of the immunoreactivity in neuronal processes was seen in the hippocampal CA1 sector 48 h after ischemia. Seven days after ischemia, a marked loss of parvalbumin-immunoreactive interneurons was observed in the hippocampal CA1 and CA3 sectors. Furthermore, reduced staining in the dentate granular and molecular layers was observed. MAP2-immunoreactive pyramidal neurons in the hippocampus were unchanged up to 48 h after ischemia. Seven days after ischemia, a severe loss of MAP2 immunoreactivity was found in the hippocampal CA1 and CA3 neurons and dentate hilar neurons. However, scattered CA1 neurons, most likely interneurons, preserved MAP2 immunoreactivity. The results demonstrate that transient cerebral ischemia can cause a loss of parvalbumin-immunoreactive interneurons in the hippocampus. Furthermore, some interneurons seem to lose parvalbumin synthesis. Although dentate granule cells are resistant to ischemia, considerable reductions of afferent input was suggested by parvalbumin staining.

Animals↗

PubMed1994

Induction of heat shock protein 70 and glial fibrillary acidic protein in the postischemic gerbil hippocampus.

Immunohistochemical changes of heat shock protein 70 (HSP 70) and glial fibrillary acidic protein (GFAP) were investigated in the gerbil hippocampus 1 h-7 days after 10 min of cerebral ischemia. Transient cerebral ischemia caused HSP 70 expression in GFAP-positive astrocytes in a delayed fashion, as compared with a rapid induction in vulnerable neurons such as hilar neurons. The present results may offer clues to elucidate the mechanisms of ischemic neuronal damage.

Animals↗

PubMed1994

Alteration of muscarinic acetylcholine binding sites in the postischemic brain areas of the rat using in vitro autoradiography.

We studied the postischemic alteration of muscarinic acetylcholine binding sites in the rat brain using in vitro [3H]quinuclidinyl benzilate (QNB) autoradiography. Transient ischemia was induced by the occlusion of the middle cerebral artery (MCA) for 90 min and such occlusion followed by various recirculation periods of up to 4 weeks. After 90 min of ischemia followed by 3 days of recirculation, [3H]QNB binding sites were found to be significantly decreased in the cerebral cortex (P < 0.01) and lateral segment of the caudate putamen (P < 0.05), both supplied by the occluded MCA; thereafter, the binding sites decreased progressively in those ischemic foci. Moreover, 3 days after the ischemia, significant decreases of [3H]QNB binding sites were observed in the ipsilateral thalamus and the amygdala, and also in the substantia nigra 1 week after the ischemia, areas which had not been directly affected by the original ischemic insult. This postischemic phenomenon observed in the thalamus and the substantia nigra developed concurrently with 45Ca accumulation, which was detected there in our previous study. These results indicate that alteration of muscarinic acetylcholine binding sites may be involved not only in the ischemic foci, but also in the exo-focal remote areas, in which delayed neuronal degeneration due to neuronal network disturbances after the ischemia was observed. We suggest that multifocal postischemic alterations of muscarinic acetylcholine binding sites may exacerbate the clinical symptoms of patients during the chronic stage of stroke.

Acetylcholine↗

PubMed1994

Metabolic disturbances in exo-focal brain areas after cortical stroke studied by positron emission tomography.

We have reported that exo-focal delayed neuronal damage was observed in the ipsilateral thalamus and the substantia nigra of the rat brain after occlusion of the middle cerebral artery (MCA). To determine if that phenomenon also occurs in humans, we measured cerebral metabolic rates for glucose (CMRGlc) in the remote brain areas at a chronic stage after cortical infarction using 2-[18F]fluoro-2-deoxy-D-glucose and position emission tomography (PET). The subjects studied were 11 patients who were affected by unilateral cerebral infarction in the cortex supplied by MCA. There were significant decreases of CMRGlc as compared with control values (p < 0.01), not only in the cerebral cortex directly damaged by the ischemic insult, but also in the ipsilateral thalamus and in the contralateral cerebellum, areas in which no lesions had been detected by MRI or CT scan. The present study indicates that different mechanisms may be responsible for multi-focal metabolic disturbances in the remote areas after stroke. The reduction of CMRGlc in the contralateral cerebellum may be explained by the crossed cerebellar diaschisis theory and in the ipsilateral thalamus as being due to retrograde degeneration associated with the infarcted cortex. We suggest that these multi-focal brain dysfunctions caused by neuronal network disturbances may exacerbate clinical symptoms at a chronic stage of stroke.

Adult↗

PubMed1994

Autoradiographic analysis of second-messenger and neurotransmitter receptor systems in the exo-focal remote areas of postischemic rat brain.

We studied the chronological changes of protein kinase C (PKC) and muscarinic acetylcholine receptor binding activities of the rat brain which were determined by using [3H]phorbol 12,13-dibutyrate (PDBu) and [3H]quinuclidinyl benzilate (QNB) autoradiographic methods, respectively, after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion, followed by different periods of recirculation. After the ischemic insult followed by 3 h of recirculation, [3H]PDBu binding sites were found to be significantly decreased in the cerebral cortex and lateral segment of the caudate putamen, both supplied by the occluded MCA; thereafter, the binding sites decreased progressively in those ischemic foci. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, a significant decrease of [3H]QNB binding sites was first detected in those ischemic foci. Moreover, 3 days after ischemic insult, both [3H]PDBu and [3H]QNB binding sites were concurrently reduced in the ipsilateral thalamus and 1 week after the ischemia, in the substantia nigra, in which both areas had not been directly affected by the original ischemic insult. These alterations of PKC in the postischemic brain areas developed concurrently with 45Ca accumulation, which was detected in our previous study. These results suggest that postischemic alterations of second-messenger (PKC) and neurotransmitter receptor systems were involved not only in the ischemic foci due to ischemia-induced energy failure, but also in the exo-focal remote areas prior to the histologic changes where neuronal damage might be caused by transsynaptic delayed degeneration.

Animals↗

PubMed1994

Ischemic tolerance and extracellular amino acid concentrations in gerbil hippocampus measured by intracerebral microdialysis.

Preconditioning of the brain with sublethal ischemia induces tolerance to subsequent longer periods of ischemia. To elucidate the role of excitatory and inhibitory amino acids in the induction of ischemic tolerance, we measured the extracellular concentrations of the amino acids in the gerbil hippocampus with intracerebral microdialysis. Mongolian gerbils were subjected to 3 min of forebrain ischemia 4 days after preconditioning with 2 min of ischemia or sham operation. Microdialysis probes were implanted into the hippocampus before the second ischemia and the amino acid concentrations in the dialysates were measured with HPLC. During and immediately after 3 min of ischemia without preconditioning, the concentrations of glutamate, glycine, gamma-aminobutyric acid, and taurine, but not glutamine, increased significantly. The increased amino acid levels rapidly returned to baseline after reperfusion. Preconditioning of the brain did not alter the amount of any amino acid released during and after the second ischemia. The excitotoxic index also unchanged in the preconditioned hippocampus. Thus, the results clearly show that ischemic tolerance is not induced through the alteration of the amounts of excitatory and inhibitory amino acids released during subsequent ischemia.

Amino Acids↗

PubMed1994

Regional changes in [3H]inositol 1,4,5-triphosphate binding in the gerbil brain following repeated sublethal ischemia.

We investigated the regional changes in [3H]inositol 1,4,5-triphosphate (IP3) binding in the brain following ischemia using in vitro autoradiography. Three 2-min ischemic insults at 1-hr intervals and a 6-min period of ischemia were induced in gerbils and they were killed after 1, 4, and 28 days. Normal animals had high [3H]IP3 binding in the CA1 subfield of the hippocampus and the striatum. The binding in the CA1 decreased strikingly after both 6-min ischemia and three 2-min ischemic insults. The [3H]IP3 binding also decreased in the lateral striatum after three 2-min ischemic insults but not after 6 min of ischemia. Histological observations confirmed neuronal damage to these areas of reduced binding. By contrast, we found a marked increase in [3H]IP3 binding in the ventral thalamus 28 days after three 2-min ischemic insults. Histological observations with Nissl staining revealed an accumulation of fine granular deposits there. Thus, repeated ischemic insults produced more extensive neuronal damage and changes in [3H]IP3 binding than a single equivalent period of ischemia. The increased [3H]IP3 binding in the thalamus coincidentally with an accumulation of Nissl-positive granules at the chronic stage after repeated ischemia is of considerable interest.

Animals↗

PubMed1994

Structural basis of potent antiperoxidation activity of the triterpene celastrol in mitochondria: effect of negative membrane surface charge on lipid peroxidation.

The structural basis of the potent inhibitory effect of the triterpene celastrol on lipid peroxidation of rat liver mitochondria initiated by adenosine 5'-diphosphate (ADP) and Fe2+ was studied in comparison with the effects of its analogs, pristimerin and acetylcelastrol. The dienone-phenol moiety and the anionic carboxyl group of celastrol were concluded to be important for their antiperoxidative action: The former moiety directly scavenges radicals and the latter donates the membrane with a negative surface charge, making it more resistant to peroxidation. Celastrol is suggested to inhibit the peroxidation of the outer and inner mitochondrial membrane by direct radical scavenging, and also to prevent the attack of oxygen radicals on the inner membrane by increasing its negative surface charge.

Adenosine Diphosphate↗

PubMed1994

Reduction of nerve growth factor receptor immunoreactivity in ischaemic gerbil hippocampal CA1 neurons after treatment with L-threo-3,4-dihydroxyphenylserine (DOPS).

Nerve growth factor (NGF) synthesis in cultured mouse L-M fibroblast and astroglial cells can be increased after the treatment with L-threo-3,4-dihydroxyphenylserine (DOPS). Since the increase of NGF is not blocked by the treatment with decarboxylase inhibitor, DOPS may have direct effect to increase the NGF content. NGF and its receptor (NGFR) are suggested to play an important role in the neuronal survival and regeneration under pathologic conditions. In this study, we studied a possible protective effect of DOPS against the hippocampal CA1 cell death after transient forebrain ischaemia in gerbils in relation to the change of NGFR immunoreactivity. We found that treatment with DOPS (300 mg kg-1) in combination with a decarboxylase inhibitor (benserazide, 10 mg kg-1) protected ischaemic hippocampal CA1 cell against delayed neuronal death (neuronal density = 125 +/- 24 mm-1) as compared to the treatment with vehicle (49 +/- 11 mm-1) (p < 0.01). The immunoreactivity for NGFR was scarcely present in the sham-control CA1 area but was induced from 1 h and markedly expressed at 7 days after recirculation in the vehicle group. However, it was slightly and transiently induced from 8 h to 2 days in the DOPS plus benserazide treated group. These data suggest that the protective role of DOPS on the ischaemic hippocampal CA1 cells may act through the NGF and its receptor system.

Animals↗

PubMed1994

Effects of vinconate and pentobarbital against postischemic alterations in spirodecanone binding sites in the gerbil brain.

We investigated the effects of vinconate and pentobarbital against the alterations in spirodecanone binding in the gerbil striatum and hippocampus 5 h and 7 days after 10 min of cerebral ischemia, using receptor autoradiography. Vinconate and pentobarbital were given intraperitoneally 10 and 30 min prior to ischemic insult, respectively. The spirodecanone binding in vehicle-treated gerbils subjected to ischemia was unchanged in the brain 5 h after recirculation, compared with that in sham-operated animals. Seven days after ischemia, a significant elevation in the spirodecanone binding was observed in the striatum and the stratum radiatum of the hippocampal CA1 sector and the hippocampal CA3 sector of the vehicle-treated animals. Other regions showed no significant change in the binding. Vinconate and pentobarbital showed no significant change in the striatum and hippocampus 5 h after ischemia. However, the administration of vinconate inhibited a significant elevation in the spirodecanone binding in the lateral striatum and the stratum radiatum of hippocampal CA1 sector 7 days after ischemia. Pentobarbital also prevented a significant elevation only in the lateral striatum. A histological study revealed that cerebral ischemia caused severe neuronal damage in the lateral striatum and hippocampal CA1 and CA3 sectors. However, ischemic neuronal damage was not observed in the dentate gyrus. An immunohistochemical study also showed that numerous reactive astrocytes were evident in the hippocampus, particularly in the hippocampal CA1 sector, 7 days after ischemia. The present study demonstrates that cerebral ischemia can cause a conspicuous elevation in spirodecanone binding in the striatum and hippocampus. They also suggest that the postischemic elevation in the spirodecanone binding is partly prevented by treatment with vinconate and pentobarbital. These results suggest that the postischemic elevation in spirodecanone binding sites may reflect expression of reactive astrocytes.

Animals↗

PubMed1994

The protective effect of L-threo-3,4-dihydroxyphenylserine on ischemic hippocampal neuronal death in gerbils.

BACKGROUND AND PURPOSE: L-Threo-3,4-dihydroxyphenylserine (DOPS) is reported to increase the nerve growth factor (NGF) synthesis in cultured mouse L-M fibroblast and astroglial cells, and this effect is not blocked by treatment with decarboxylase inhibitor. NGF is suggested to play an important role in neuronal survival and regeneration under pathological conditions. We evaluated the possible protective effect of DOPS against hippocampal CA1 cell death after transient forebrain ischemia in gerbils. METHODS: Male mongolian gerbils were treated with DOPS (30, 100, or 300 mg/kg IP) plus benserazide (10 mg/kg IP) (n = 28) or vehicle (n = 7) before 3.5 minutes of forebrain ischemia. For histopathologic study, the animals were decapitated 7 days after recirculation, and neuronal density of the hippocampal CA1 area was counted after cresyl violet staining. For immunohistochemical study, another group of gerbils (n = 34) was recovered for 1, 3, and 8 hours and 1, 2, and 7 days, when they were decapitated. The brain sections were stained against NGF, NGF receptor, and HSP70 using the avidin-biotin-peroxidase method. RESULTS: Preservation of the hippocampal CA1 cells was found in the brains treated with 300 mg/kg DOPS plus benserazide (neuronal density, 125 +/- 24 cells per millimeter) compared with the vehicle-treated ones (49 +/- 11 cells per millimeter) (P < .01). The immunoreactive NGF was greatly reduced from 3 hours after recirculation in the vehicle group, but it was much less reduced in the 300-mg/kg-DOPS-plus-benserazide group as compared with the vehicle group. The immunoreactivity for NGF receptor was gradually induced from 1 hour after recirculation with the peak at 1 day in the vehicle group, but it was only slightly induced at 8 hours in the 300-mg/kg-DOPS-plus-benserazide group. HSP70 immunoreactivity was also induced from 3 hours with the peak at 1 day in the vehicle group. However, in the 300-mg/kg-DOPS-plus-benserazide group, the induction of HSP70 was found from 8 hours and was much less intensive. CONCLUSIONS: Treatment with DOPS is protective to the ischemic hippocampal CA1 cells, and the NGF-receptor system may play a role in this protective effect of DOPS.

Animals↗

PubMed1994

Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion.

BACKGROUND AND PURPOSE: Neutrophils have been implicated in the pathogenesis of ischemia-reperfusion injury. The aim of the present study was to evaluate the correlation between neutrophil infiltration into ischemic tissues and brain injury after transient focal ischemia. METHODS: We evaluated the effects of depletion of circulating neutrophils by administration of an antineutrophil monoclonal antibody (RP3) on brain edema formation, infarct size, and neutrophil infiltration (myeloperoxidase [MPO]-quantified) in rats with 1 hour of middle cerebral artery (MCA) occlusion. RESULTS: In the cerebral cortex perfused by the anterior cerebral artery (ACA area), there was a significant increase in MPO activity only 24 hours (P < .05) after reperfusion. In the cerebral cortex perfused by the middle cerebral artery (MCA area) and caudate putamen, MPO activity was significantly increased at 12 (MCA area, P < .01; caudate putamen, P < .05), 24 (MCA area, P < .05; caudate putamen, P < .01), and 72 hours (MCA area, P < .01; caudate putamen, P < .05) and returned to near-normal level by 168 hours after reperfusion. Brain MPO activity after transient MCA occlusion correlated well with the appearance of neutrophils. Depletion of neutrophils by RP3 treatment completely inhibited the increase in MPO activity in the ischemic brain after 24 hours of reperfusion. In addition, treatment with RP3 significantly attenuated the postischemic increase in brain water content at 24 hours after reperfusion. RP3 also significantly reduced the size of infarct area. CONCLUSIONS: These results indicate that the increase in brain MPO activity after transient focal ischemia virtually reflects the neutrophil infiltration and that neutrophil infiltration into the ischemic brain is implicated in postischemic brain injury.

Animals↗

PubMed1994

Expression of cytokines in brain lesions in subacute sclerosing panencephalitis.

We analyzed frozen brain specimens from three patients with subacute sclerosing panencephalitis (SSPE) for the presence of interleukin (IL)-1 beta, IL-2, IL-6, tumor necrosis factor (TNF), lymphotoxin (LT), and interferon (IFN)-gamma using immunocytochemical techniques. We detected these cytokines in SSPE brain lesions demonstrating extensive cellular infiltrates, demyelination, and gliosis. Double-label immunocytochemistry, using cell-specific markers, showed that positive immunoreactivity for these cytokines was present on both infiltrating cells and resident brain cells. We also found IL-6, TNF, and IFN-gamma at lower levels in brain tissue from a patient with progressive multifocal leukoencephalopathy. In contrast, normal control brain sections showed no reactivity for any of the cytokines. These findings indicate that IL-1 beta, IL-2, IL-6, TNT, LT, and IFN-gamma may be produced in SSPE lesions and may be involved in the lesion pathogenesis of SSPE.

Adult↗

PubMed1994

[A trial use of prostaglandin E1 for prevention of hepatic veno-occlusive disease after allogeneic bone marrow transplantation].

We performed retrospective analysis of hepatic veno-occlusive disease (VOD) in 57 cases with leukemia after allogeneic bone marrow transplantation (BMT). Prostaglandin E1 (PGE1) was used to prevent VOD in 8 cases at a dose of 0.3 micrograms/kg/hr from day -8 to day 30. No VOD was noted in the PGE1 group, while the incidence of VOD was 8/49 (16.3%) in the non PGE1 group. In twelve patients with pretransplant liver dysfunction, VOD was noted in 0/3 in the PGE1 group and 4/9 (44.4%) in the non PGE1 group, respectively. However, prophylactic effects of PGE1 on VOD is not significant in this study, so further studies are needed to determine the efficacy of PGE1. One of 8 patients with PGE1 prophylaxis had edema and erythema on extremities, however, severe toxicity was not experienced.

Adolescent↗

PubMed1994

[A combination chemotherapy of mitoxantrone, etoposide, carboplatin, and prednisolone (MECP) in recurrent or refractory non-Hodgkin's lymphomas].

Twenty-two patients with recurrent or refractory non-Hodgkin's lymphoma were treated with a combination chemotherapy of mitoxantrone, etoposide, carboplatin, and prednisolone (MECP). Of 22 evaluable patients, 11 (50%) responded to MECP and 7 (32%) achieved complete remission. Particularly in relapsed cases, 9 (75%) responded and 6 (50%) achieved complete remission. Myelosuppression was the major toxicity. Thirteen patients (59%) experienced WBC counts under 1,000/microliters, and thrombocytopenia under 50,000/microliters was seen in 12 patients (55%). During myelosuppression, 2 patients developed sepsis and 1 showed intestinal bleeding. Other gastrointestinal toxicities were well tolerated. There was no death due to chemotherapy. These results show that MECP is a well-tolerated treatment regimen, and effective for recurrent or refractory non-Hodgkin's lymphomas.

Administration, Oral↗