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Biomedical subjects

S Okamoto

Publications and source records attributed to S Okamoto.

At least 109 records · Page 6Linked to original sources
PubMed2001

[Systemic non-Hodgkin lymphoma initially presented with visual disturbance due to intrasellar lymphoma--a case report].

A case with systemic non-Hodgkin lymphoma involving the sella turcica and kidney is reported. A 69-year-old man presented with a progressive two month history of visual disturbance and headache. Neurological examination revealed bilateral visual disturbance and right optic atrophy. MRI showed a contrast-enhancing mass in the sella turcica. The tumor extended to the right optic nerve. Without extensive studies for systemic disease, the patient immediately underwent transsphenoidal surgery. The slightly firm, fibrous and vascular-rich tumor was subtotally removed. The histopathological examination revealed a malignant lymphoma, diffuse-large-cell type with B-cell phenotype. The postoperative course was uneventful and the patient's symptoms subsided gradually. The patient received radiation therapy and the tumor disappeared. Postoperative CT examinations of the abdomen and pelvis revealed a large mass at the upper portion of the left kidney. Ga-scan also suggested the mass to be consistent with the abdominal CT. However, the patient suddenly died of acute heart failure with unknown cause just before starting chemotherapy for systemic lymphoma. Patients presenting primary central nervous system lymphoma (PCNSL) may have systemic non-Hodgkin lymphoma. To exclude systemic non-Hodgkin lymphoma, systemic investigation is essential for the initial management of patients presenting PCNSL.

Aged↗
PubMed2001

[Dural arteriovenous fistula of the anterior cranial fossa associated with occlusion of the internal carotid artery: a case report].

We reported a case with dural arteriovenous fistula (dAVF) of the anterior cranial fossa associated with occlusion of the left cervical internal carotid artery. A 73-year-old man was admitted with total aphasia and right hemiparesis. Computed tomography showed an ischemic lesion of the left cerebral hemisphere and old infarction of the left occipital lobe. Angiography revealed occlusion of the left cervical internal carotid artery and dAVF of the anterior cranial fossa, fed by the left middle meningeal and the right anterior ethmoidal artery. Follow-up angiography revealed spontaneous recanalization and severe arteriosclerosis of the left internal carotid artery. After marked improvement of neurological deficits, the patient underwent surgical clipping of the draining veins to occlude the dAVF of the anterior cranial fossa. We speculated that marked development of the collateral circulation from the external carotid system might result in the occurrence of dAVF of the anterior cranial fossa.

Aged↗
PubMed2001

[Follicular lymphoma in two brothers].

Two brothers, whose parents had a history of exposure to atomic bomb radiation, developed non-Hodgkin's lymphoma. The younger brother, a 48-year-old man, was diagnosed as having follicular small-cleaved cell lymphoma in October, 1996. He had extranodal lymphoma involvement of the right kidney, bone marrow and skin, in addition to generalized lymphadenopathy. He was treated with intermittent COP chemotherapy, and good control of the lymphoma was obtained. The elder brother, aged 50 years, was diagnosed as having follicular mixed cell lymphoma in May, 1998. He also had extranodal lymphoma involvement of the right parotid gland and bone marrow, as well as generalized lymphadenopathy. After one course of CHOP chemotherapy, he developed paresis of the lower legs and was found to have a mass at the Th5-6 vertebrae by CT scan. After four courses of CHOP chemotherapy followed by ESHAP chemotherapy and radiotherapy, he achieved complete remission, and has since been well. Follicular lymphoma occurring among siblings is rare. Further cytogenetic and molecular studies may provide a better understanding of its etiology.

Antineoplastic Combined Chemotherapy Protocols↗
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↗
PubMed2001

[Allogeneic stem cell transplantation].

Over the last two decades, four major therapeutic approaches have dramatically changed the prognosis in chronic myelogenous leukemia(CML). Those include allogeneic stem cell transplantation, interferon-alpha based regimen, donor-leukocyte infusions, and the revolutionary BCR/ABL tyrosine kinase inhibitor such as STI571. Each modality has exploited and targeted different aspects of CML biology, and is associated with different risk-benefit ratios. In this section, we update the results of both related and unrelated donor transplantation, donor lymphocyte infusions, and non-myeloablative stem cell transplantation in CML in comparison with the other treatment modalities.

Adult↗
PubMed2001

The actin-depolymerizing factor destrin has an actin-stabilizing domain.

Destrin is a 19 kDa actin-depolymerizing protein of the ADF-cofilin family. Destrin was digested with trypsin to a structurally stable 9.2 kDa fragment that contains the actin-binding sequence. The purified 9.2 kDa fragment has an actin filament stabilizing activity, rather than an actin filament depolymerizing activity. The deleted region is probably essential for the actin filament depolymerizing activity of intact destrin. Surprisingly, the 9.2 kDa fragment also has an assembly-promoting activity in the absence of ATP.

Actin Depolymerizing Factors↗
PubMed2001

[Pulmonary involvement, pleural effusion, and electrocardiographic abnormality in hypereosinophilic syndrome].

A 47-year-old man was admitted to our hospital with complaints of cough and shortness of breath. Chest radiography showed infiltration of the right lung and left pleural effusion, the eosinophil count increased notably in the peripheral blood, sputum, and pleural effusion. Transbronchial lung biopsy revealed the invasion of eosinophils like eosinophilic pneumonia. Heart failure easily developed in this patient after the intravenous infusion. Myocardial involvement was suspected, and hypereosinophilic syndrome was diagnosed. After prednisolone was administered, the peripheral blood eosinophil count normalized rapidly, and subsequently, the pleural effusion and infiltration shadows in the lung disappeared.

Anti-Inflammatory Agents↗
PubMed2000

Development of plasmin and plasma kallikrein selective inhibitors and their effect on M1 (melanoma) and HT29 cell lines.

trans-4-Aminomethylcyclohexanecarbonyl-Tyr(O-Pic)-octylamide (YO-2) inhibited plasmin (PL) selectively, while trans-4-aminomethylcyclohexanecarbonyl-Phe-4-carboxymethylanili de (YO-1) inhibited plasma kallikrein (PK). YO-2 induced apoptosis of M1 (melanoma) cell line and HT29 colon carcinoma cells during 24 h through activation of caspase-3, while YO-1 did not affect either cell line even during 48 h.

Antineoplastic Agents↗
PubMed2000

Preparation of titanated alkoxyallenes from 3-alkoxy-2-propyn-1-yl carbonates and (eta(2)-Propene)Ti(O-i-Pr)(2) as an efficient ester homoaldol equivalent

3-Alkoxy-2-propyn-1-yl carbonates (2) react with a divalent titanium reagent (eta(2)-propene)Ti(O-i-Pr)(2) to afford titanated alkoxyallenes 1 which, in turn, react with aldehydes regiospecifically to provide the corresponding gamma-addition products in good to excellent yields, thus affording a convenient method for synthesizing gamma-hydroxy esters 3 and/or gamma-butyrolactones 4.

Journal Article↗
PubMed2000

Selective inhibition of trypsin by (2R,4R)-4-phenyl-1-[Nalpha-(7- methoxy-2-naphthalenesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid.

Evidence is accumulating indicating that trypsin stimulates divergent cellular reactions through the proteinase-activated receptor, in addition to its role as the digestive enzyme. In this report, we introduce (2R,4R)- 4-phenyl-1-[N(alpha)-(7-methoxy-2-naphthalenesulfonyl)-l-arginyl]- 2-p iperidinecarboxylic acid as a potent and selective trypsin inhibitor. The agent inhibited trypsin competitively with the K(i) value of 0. 1 micrometer. It inhibited thrombin weakly (K(i) = 2 micrometer) and did not inhibit plasmin, plasma kallikrein, urokinase, and mast cell tryptase (K(i) values for these enzymes are >60 micrometer). Comparative studies with several established proteinase inhibitors revealed that the compound was the first small molecular weight trypsin inhibitor without tryptase inhibitory activity. A docking study has provided a plausible explanation for the molecular mechanism of the selective inhibition showing that the agent fits into the active site of trypsin without any severe collision but that it comes into clash at the 4-phenyl group of piperidine ring against the "60-insertion loop" of thrombin and at the 7-methoxy-2-naphthalenesulfonyl group against Gln(98) of tryptase.

Amino Acid Sequence↗
PubMed2000

Antiapoptotic role of the p38 mitogen-activated protein kinase-myocyte enhancer factor 2 transcription factor pathway during neuronal differentiation.

Myocyte enhancer factor 2 (MEF2) is in the MADS (MCM1agamous-deficiens-serum response factor) family of transcription factors. Although MEF2 is known as a myogenic factor, the expression pattern of the MEF2 family of genes (MEF2A-D) in developing brain also suggests a role in neurogenesis. Here we show that transfection with MEF2C, the predominant form in mammalian cerebral cortex, induces a mixed neuronal/myogenic phenotype in undifferentiated P19 precursor cells. During retinoic acid-induced neurogenesis of these cells, a dominant negative form of MEF2 enhances apoptosis but does not affect cell division. The mitogen-activated protein kinase p38alpha activates MEF2C. Dominant negative p38alpha also enhances apoptotic death of differentiating neurons, but these cells can be rescued from apoptosis by coexpression of constitutively active MEF2C. These findings suggest that the p38alpha/MEF2 pathway prevents cell death during neuronal differentiation.

Apoptosis↗
PubMed2000

NK cells cause liver injury and facilitate the induction of T cell-mediated immunity to a viral liver infection.

NK cells are a relatively rare cell population in peripheral lymphoid organs but are abundant in the liver, raising questions as to their function in immune responses to infections of this organ. To investigate this, cell-mediated immunity to viral liver infection induced by a type 5, replication-defective, adenovirus was examined. It is shown that NK cells in the absence of T cells cause hepatocyte apoptosis in virus-infected livers associated with an increase in liver enzymes in the serum. Concomitantly, NK cells induce production of IFN-gamma, inhibitable by their elimination before infection. NK cells are shown to be necessary for optimal priming of virus-specific T cells, assessed by delayed-type hypersensitivity response and CTL activity, consistent with their ability to secrete IFN-gamma. The conclusion is drawn that NK cells mediate two important functions in the liver: they induce cell death in the infected organ and concomitantly stimulate the induction of T cell-mediated immunity by release of IFN-gamma.

Adenoviridae Infections↗
PubMed2000

Immunomodulation with FK506 around the time of intravenous re-administration of an adenoviral vector facilitates gene transfer into primed rat liver.

Although adenoviruses are an attractive vehicle for gene transfer into tissues including various tumors, in vivo adenoviral administration elicits a neutralizing antibody response which eliminates or substantially reduces the efficacy of subsequent treatments. Transiently immunosuppressive strategies at the time of initial adenoviral exposure have shown to prevent the formation of neutralizing antibodies and permit the successful adenoviral readministration in animals. Initial treatment in humans may, however, correspond to adenoviral readministration into animals, because the exposure to wild-type adenoviruses is common in humans. In the present study, we infused Adex1CAlacZ adenoviruses carrying the lacZ gene into the tail vein of rats, and examined whether a transient treatment with the immunosuppressant FK506 around the time of i.v. readministration of adenoviruses could induce the re-expression of the lacZ gene in animals primed with adenoviruses. Although i.v. infusion of adenoviruses carrying the lacZ gene resulted in transiently high levels of transgene expression in rat liver, i.v. reinfusion of adenoviruses failed to induce detectable levels of transgene expression. Conversely, when animals were treated transiently with FK506 around the time of adenoviral reinfusion, development of neutralizing antibodies and antigen-specific T cell proliferation in response to adenoviral reinfusion were significantly suppressed, and re-expression of the transgene was achievable.

Adenoviridae↗
PubMed2000

Central leptin suppresses splenic lymphocyte functions through activation of the corticotropin-releasing hormone-sympathetic nervous system.

Leptin is one of the key afferent signals that regulate food intake and energy expenditure by acting on specific receptors in the hypothalamus. Recently, leptin was reported to activate the peripheral immune system by acting directly on lymphocytes. To elucidate the brain-mediated participation of leptin in the modulation of peripheral immune functions, we examined the effects of intracerebroventricular (icv) injection of murine recombinant leptin on the proliferative response to Concanavalin A (ConA response) of splenic lymphocytes in rats. The ConA response of splenic lymphocytes was markedly reduced 30 min after icv injection of leptin. The suppressive effect of leptin was abolished completely either by surgical severing of the splenic nerves or by icv injection of an antibody against corticotropin-releasing hormone (CRH), but only partially by an anti-urocortin antibody. Icv injection of CRH and urocortin also suppressed the ConA response of splenic lymphocytes, and the effect of urocortin was prevented by the anti-CRH antibody, while that of CRH was not prevented by the anti-urocortin antibody. These results suggest that leptin suppresses peripheral lymphocyte functions, in contrast to the direct activating effects, indirectly through the activation of the CRH (urocortin)-sympathetic nervous system.

Animals↗
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

Fas- and tumor necrosis factor receptor 1-dependent but not perforin-dependent pathways cause injury in livers infected with an adenovirus construct in mice.

Intravenous injection of type 5 adenovirus, deleted in the E1 and E3 regions, is shown to result in expression of viral antigens in the liver, initiating lymphocyte infiltration and liver injury. Following this infection, induction of Fas ligand (FasL), tumor necrosis factor alpha (TNF-alpha), and perforin mRNA are all demonstrable in the liver, pointing to a role of respective pathways in liver injury. Making use of mice in which the genes coding for Fas, FasL, TNF receptors (TNFRs), and perforin are inactivated, as well as recombinant proteins that inhibit Fas- and TNF-alpha-mediated apoptosis, it is shown that a functional perforin-mediated mechanism is not obligatory for cellular infiltration and progression of liver injury. In contrast functional Fas- and TNF-alpha-mediated mechanisms were found to be essential for liver injury to occur. Results are presented demonstrating that signaling through TNFR1, but not TNFR2, is involved in TNF-alpha-mediated liver damage. The conclusion is drawn that although perforin mRNA is induced in the virus-infected liver, Fas- and TNF-alpha-mediated mechanisms constitute the principal pathways by which the cell-mediated immune system causes acute liver injury.

Adenoviridae↗
PubMed2000

Proinsulin C peptide obviates sympathetically mediated suppression of splenic lymphocyte activity in rats.

AIMS/HYPOTHESIS: To investigate whether proinsulin C peptide influences sympathetic nerve activity directly or indirectly through parasympathetic nerve activity. METHODS: The proliferative response of splenic lymphocytes to Concanavalin A (ConA response) which is known to be suppressed by subjection of rats to footshock or intracerebroventricular injection of corticotropin-releasing factor through sympathetic nerve activation was measured. Effect of C peptide alone or before subjection to footshock or injection of corticotropin-releasing factor was examined. RESULTS: Intraperitoneal injection of C peptide was without effect on the basal ConA response, while subjection to footshock or injection of corticotropin-releasing factor lowered it. In contrast, prior injection of C peptide obviated the footshock and corticotropin-releasing factor-induced suppression of the response. When given intracerebroventricularly, C peptide was also effective at much smaller doses. Prior injection of atropine cancelled the C-peptide effects. CONCLUSION/INTERPRETATION: Our results indicate that C peptide counteracts the sympathetic nerve-mediated suppression of splenic lymphocyte proliferation in an atropine-sensitive manner. Thus, C peptide probably activates the parasympathetic nervous system through the afferent mechanism, that in turn antagonizes the sympathetic nerve-mediated suppression of splenic lymphocyte functions.

Animals↗