Biomedical subjects

T Koike

Publications and source records attributed to T Koike.

At least 325 records · Page 18Linked to original sources

PubMed1997

Effective high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in a patient with the aggressive form of cytophagic histiocytic panniculitis.

A 20-year-old Japanese man developed generalized, subcutaneous, painless nodules, fever, abnormal liver function, serosal effusions, hepatosplenomegaly, lymphadenopathy and anemia. Skin biopsies revealed lobular panniculitis with a morphologically benign histiocytic infiltration and prominent phagocytosis. Atypical T lymphocytes were also present in the skin and liver. The diagnosis given was aggressive cytophagic histiocytic panniculitis (CHP) or aggressive subcutaneous panniculitic T cell lymphoma (SPTCL). He received cyclophosphamide, doxorubicin, and vincristine on day 1, prednisolone on days 1-5, and etoposide on days 1, 3 and 5 (CHOP-E), with the support of granulocyte colony-stimulating factor. This regimen was repeated every 2 weeks and complete clinical remission (CCR) was attained after three cycles of CHOP-E. As the clinical course of aggressive CHP is recurrent and often fatal, he was given high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (APBSCT), after five cycles of CHOP-E. He has remained in CCR for 12 months after APBSCT. High-dose chemotherapy followed by APBSCT is considered to be one of the most beneficial therapies for patients with aggressive CHP and aggressive phase SPTCL.

Adolescent↗

PubMed1997

Primary familial polycythaemia associated with a novel point mutation in the erythropoietin receptor.

Primary familial and congenital polycythaemia (PFCP) is a rare disease characterized by congenital erythrocytosis inherited in an autosomal dominant fashion. Recently, mutations in the erythropoietin receptor (EpoR) have been identified in PFCP families. We describe a Japanese family with an autosomal dominant inheritance of PFCP. An in vitro colony assay demonstrated hypersensitivity of erythroid progenitors to erythropoietin (Epo) in affected family members. Sequence analysis of RT-PCR products amplified from the C-terminal region of EpoR transcripts in affected family members revealed that they were all heterozygous for C and T bases at position 5986, which suggested a genetic mutation (C to T) on one allele of EpoR. This mutation gave rise to a translation termination codon TAG at amino acid 435. Thus, the resulting EpoR is a truncated protein product lacking all 74 amino acids downstream of the mutation. To date, all genetic mutations affecting a family with PFCP, including this one, have been located in the cytoplasmic negative regulatory region of the EpoR. All mutations gave rise to truncated Epo receptors between Tyrosine 427 and Tyrosine 455. The phosphotyrosines in this region of EpoR have been demonstrated to be binding sites for SHP-1 phosphatase. Therefore PFCP is presumably brought about as a result of genetic mutations which cause the loss of the SHP-1 binding site in the cytoplasmic region of EpoR.

Base Sequence↗

PubMed1997

Protection by alpha2-macroglobulin of tissue plasminogen activator against inhibition by plasminogen activator inhibitor-1.

Tissue plasminogen activator (tPA) is widely used in the treatment of acute myocardial infarction (MI). However, its thrombolytic efficacy does not correlate with the dose administered. The interactions between tPA, alpha2-macroglobulin (alpha2-M), and plasminogen activator inhibitor-1 (PAI-1) were investigated both in vitro and in patients undergoing tPA therapy for MI in an attempt to identify variables that might affect the clinical efficacy of tPA. Purified alpha2-M (5.4 mg/ml) protected 16.0% or 22.4% of tPA (12.5 IU/ml) activity from inhibition by PAI-1 at 4 or 8 IU/ml in vitro. Of nine patients treated with 5-20 mega IU of tPA for MI, the plasma activity of tPA remained increased for 15-30 min after the cessation of infusion in eight; the patient who failed to exhibit a persistent increase in tPA activity had a low plasma concentration of alpha2-M. Total tPA activity, derived from the area under the activity-versus-time curve (AUC), showed a significant inverse correlation with the ratio of the plasma PAI-1 activity to the plasma alpha2-M concentration. Total tPA activity did not correlate with plasma PAI-1 activity or plasma alpha2-M concentration alone. Results suggest that alpha2-M, by binding to tPA, protects the latter against inhibition by PAI-1.

Aged↗

PubMed1997

Oxidized low-density lipoprotein (Ox-LDL) but not LDL aggravates the manifestations of experimental antiphospholipid syndrome (APS).

Ox-LDL is thought to play a major role in atherogenesis. The mechanisms mediating the deleterious influences of Ox-LDL include foam cell formation and cell cytotoxicity. The production of anti-Ox-LDL antibodies results in the formation of immune complexes which are taken up at enhanced rate by macrophages, leading to foam cell formation. APS is characterized by repeated venous and arterial thromboembolic phenomena, recurrent fetal loss and thrombocytopenia, associated with the presence of antibodies to negatively charged phospholipids (aPL) (i.e. cardiolipin, phosphatidylserine). Phospholipids bear structural resemblance to LDL, and several studies have indeed proved that aPL display cross-reactivity with anti-Ox-LDL antibodies. In this study we assessed the capacity of oxidized and native forms of LDL to aggravate the clinical picture of experimentally induced APS in naive mice. Mice were actively immunized intradermally with anticardiolipin antibodies and developed a clinical picture resembling APS in humans. Subsequently, the mice were infused with either Ox-LDL, native LDL or PBS, and similar regimens were applied to controls. APS mice infused with Ox-LDL were found to exhibit a significantly more severe form of the disease in comparison with native LDL- and PBS-infused mice, expressed by lower platelet counts (261,000/mm3, 535,000/mm3 and 455,000/mm3, respectively), longer activated partial thromboplastin time (aPTT) (99 +/- 12 s, 63 +/- 8 s and 74 +/- 8 s, respectively) and higher fetal resorption rates (72.7%, 34.4% and 32.6%, respectively). The results of this study show that Ox-LDL, compared with native LDL, aggravates the clinical manifestations of experimental APS and suggest that cross-reactivity of Ox-LDL with phospholipids may provide a pathogenic explanation for this effect.

Animals↗

PubMed1997

Serum levels of soluble Fas/APO-1 (CD95) and its molecular structure in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases.

There are two major forms of the Fas molecule, membranous Fas and soluble Fas (sFas). To clarify the clinical significance of sFas in autoimmune diseases, we designed a sandwich ELISA to determine serum concentrations of sFas and its molecular structure, and we then analysed the correlation between levels of sFas and laboratory findings in patients with SLE and other autoimmune diseases. The levels of serum sFas were significantly higher in SLE patients than in subjects with other autoimmune diseases and in healthy donors, and the frequency of a positive serum sFas was much greater in SLE patients with high SLE disease activity index scores than in those with low scores. In addition, sFas-positive SLE patients showed a significant difference in various laboratory parameters from sFas-negative SLE patients. Serial measurements of serum sFas levels in SLE patients with active disease revealed that the elevated level of sFas dramatically decreased with improvement in clinical and laboratory findings, following corticosteroid therapy. We propose that the serum level of sFas can serve as an appropriate marker for evaluating SLE disease activity. Serum sFas is heterogeneous with respect to molecular structure, thus several mechanisms are involved in the generation of sFas.

Autoimmune Diseases↗

PubMed1997

Involvement of beta 2-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages.

Anticardiolipin antibodies (aCL) in the sera of patients with antiphospholipid syndrome (APS) recognize an altered structure of beta 2-glycoprotein I (beta 2-GPI) interacting with solid-phase negatively charged phospholipids. beta 2-GPI bound to Cu2+-oxidized plasma lipoproteins, i.e. oxidized very low-density lipoprotein (oxVLDL), oxidized low-density lipoprotein (oxLDL), or oxidized high-density lipoprotein (oxHDL). beta 2-GPI inhibited in vitro uptake, i.e. cell surface binding, cellular association, and proteolytic degradation of oxLDL by murine macrophage J774A.1 cells. The binding of oxLDL to the macrophages was inhibited by the addition of polyinosinic acid (poly (I)), a competitor of the scavenger receptor, but not by another polyanionic acid, polycytidylic acid (poly (C)). Conversely, the binding of oxLDL was significantly increased by the simultaneous addition of human beta 2-GPI and monoclonal aCL derived from NZW x BXSB F1 (WB F1) mice, an animal model of APS, or anti-beta 2-GPI antibodies from BALB/c mice immunized with human beta 2-GPI. These findings indicate that beta 2-GPI may be an antiatherogenic protein and that the autoimmune response against beta 2-GPI may have a role in the development of atherosclerosis in APS.

Animals↗

PubMed1997

The best site for bronchial stapling in left and right upper lobectomies: a comparative study.

Bronchial stapling and postoperative bronchoscopy was performed in 22 left upper lobectomies (LUL) and 18 right upper lobectomies (RUL). Seven LUL cases and 15 RUL cases with staples positioned 2 bronchial rings (BR) from the entrance to the upper lobe bronchus (ULB) had no residual cartilaginous rings at the stump (RCRS). Deformity of the residual bronchus (DRB) was found in 6 of these 7 LUL cases, and 3 of these 15 RUL cases (p < 0.01), with a high rate of suffering from a severe cough. The remaining 15 LUL cases and 3 RUL cases had staples positioned 3 to 4 BR from the entrance to the ULB resulting in one or two RCRS. Only one LUL case with one RCRS was accompanied by DRB and coughing. These facts strongly imply a connection between cough and DRB. DRB was frequently seen in LUL cases with no RCRS (86%), was less likely to occur in cases with one RCRS (10%), and was absent in cases with two RCRS (p < 0.01). We conclude that bronchial staples applied during a LUL should be positioned 3 or 4 bronchial rings distal from the entrance to the left ULB.

Aged↗

PubMed1997

A wide spectrum of collagen vascular and autoimmune diseases in transgenic rats carrying the env-pX gene of human T lymphocyte virus type I.

To investigate the pathogenesis of human T lymphocyte virus type I (HTLV-I)- related diseases, the env-pX gene of HTLV-I was introduced into the germline of inbred Wistar-King-Aptekman-Hokudai rats. A wide spectrum of collagen vascular diseases was evident in the transgenic rats, including chronic destructive arthritis similar to rheumatoid arthritis, necrotizing arteritis mimicking polyarteritis nodosa, polymyositis, myocarditis, dermatitis, and chronic sialoadenitis and dacryoadenitis resembling Sjögren's syndrome in humans. Thymic atrophy with the depletion of CD4 and CD8 double-positive thymocytes was also observed. In these animals, a number of autoantibodies, including high titers of rheumatoid factor, were present in the serum. We propose that the HTLV-I env-pX gene region may play a pathogenetic role in the development of collagen vascular and autoimmune diseases associated with autoimmune phenomenon.

Animals↗

PubMed1997

Immunologic characterization and functional properties of murine antibodies raised against deleted mutants of human beta 2-glycoprotein I.

beta 2-Glycoprotein I (beta 2GPI) is a 50 kDa molecule proposed as a principal target of 'autoimmune' antiphospholipid antibodies (aPL). We have used deleted mutants (DM) representing different domains of beta 2GPI (I-IV, IV-V and V) for immunization of naive mice and studied the characteristics of the respective murine IgG preparations in comparison with affinity-purified IgG from two patients with primary antiphospholipid syndrome. Immunization with beta 2GPI and with the DM produced anti-beta 2GPI antibodies, part of which reacted with negatively charged phospholipids (PL), whereas reactivity with cardiolipin was evident only in the IgG from mice immunized with beta 2GPI. These results are consistent with the presumption that aPL are induced following the in vivo association of beta 2GPI (used for immunization) with resident negatively charged PL. Accordingly, DM which either lack the PL binding site or aPL attachment locus did not elicit, upon immunization, antibodies reactive with PL. Further, murine anti-beta 2GPI IgG and human 'autoimmune' aPL were similar, albeit not identical, in terms of DM requirement for PL binding and charge dependency. Murine antibodies and human aPL, regardless of their binding characteristics, were found to bind significantly to platelets upon their activation with thrombin and to promote platelet activation. The results of the current study emphasize the dissimilarities between human 'autoimmune' aPL and murine anti-beta 2GPI. Thus, anti-beta 2GPI antibodies to different DM as well as human aPL are capable of binding and activating human platelets provided beta 2GPI is present.

Animals↗

PubMed1997

Induction of Bip mRNA upon programmed cell death of differentiated PC12 cells as well as rat sympathetic neurons.

We have found that expression of the Bip (immunoglobulin heavy chain binding protein)/GRP78 (glucose regulated protein 78) gene is markedly enhanced specifically among the heat shock protein (HSP) 70 gene family during the neuronal cell death of PC12 (22a) cells, that is induced by removal of nerve growth factor (NGF) and blocked by a transcription inhibitor, actinomycin D. The Bip mRNA induction is suppressed when the NGF-deprivation-dependent cell death of PC12 (22a) cells is inhibited by cAMP, cycloheximide or high K+. The Ca2+ ionophore, A23187, caused neuronal cell death accompanied by up-regulation of Bip, HSP90, and HSP70 mRNAs. In addition, a chelator of intracellular Ca2+ (BAPTA) elevated Bip mRNA and induced cell death in a low Ca2+ medium. Alterations of intracellular calcium homeostasis thus appear to induce Bip mRNA expression as well as apoptosis in PC12 (22a) cells. However, release of Ca2+ from intracellular stores by thapsigargin induced Bip mRNA expression but not cell death, indicating that Bip mRNA induction is not sufficient for neuronal death. Induction of Bip mRNA in association with apoptosis was also observed for NGF-deprived sympathetic ganglion cells in primary culture. These lines of evidence suggest that selective induction of Bip mRNA may play an important role in the programmed cell death of neurons deprived of neurotrophic factors and could be a landmark of the neuronal programmed cell death.

Actins↗

PubMed1997

Diversity in the renal hemodynamic effects of dihydropyridine calcium blockers in spontaneously hypertensive rats.

Effects of dihydropyridine (DHP) Ca2+ channel blocker (CaB) on glomerular hemodynamics are controversial. We examined the effects of two DHP derivatives, benidipine hydrochloride (BDP) and nifedipine (NDP), on glomerular hemodynamics by an in vivo micropuncture method by using spontaneously hypertensive rats (SHRs). Systemic bolus infusion of BDP (4 microg/kg) or NDP (250 microg/kg) elicited comparable decreases in mean arterial blood pressure (MAP). The proximal stop-flow pressure (Psf), an indicator of glomerular capillary pressure, revealed significant decreases in BDP but nonsignificant increases in NDP. To minimize the influence of MAP or other systemic events, we monitored Psf during perinephron infusion of CaB and observed significant increases in Psf during 10(-3) M NDP perfusion and nonsignificant changes with 10(-3) M BDP. Moreover, the stability of Psf during alteration of renal perfusion pressure was significantly impaired in the nephron treated with topical NDP. These findings support the notion that CaB has diverse effects on glomerular hemodynamics, and such effects may in part be the result of different pharmacologic actions on the renal microvasculature.

Animals↗

PubMed1997

Detection of delayed cerebral vasospasm, after rupture of intracranial aneurysms, by magnetic resonance angiography.

OBJECTIVE: The goal of this study was to assess the value of magnetic resonance angiography (MRA), compared with conventional angiography, in the diagnosis and follow-up monitoring of delayed cerebral vasospasm after subarachnoid hemorrhage resulting from rupture of intracranial aneurysms. METHODS: For 32 patients undergoing examination by both MRA and conventional angiography during the period of risk for vasospasm, on the same day, the frequency and severity of and sequential changes in vasospasm were evaluated. The three-dimensional time-of-flight method was used. MRA was performed three times, i.e., before, during, and after the period of risk for vasospasm. Conventional angiography was performed twice, i.e., at admission and during the period of risk for vasospasm. Vasospasm was assessed at 22 regions of the cerebral arteries, including the bilateral anterior cerebral (A1, A2, and A3 segments), middle cerebral (M1, M2, and M3 segments), internal carotid (C1 and C2 segments), posterior cerebral (P1 and P2 segments), and posterior communicating arteries. RESULTS: Seven patients were excluded because of poor MRA images. Twenty-two of 25 patients (125 arteries) showed vasospasm in conventional angiograms. Nineteen of the 22 patients also showed vasospasm in MRA images; however, 57 arteries (45.6%) were diagnosed as showing vasospasm by MRA, and 59 (47.2%) could not be evaluated because of artifacts. For the remaining three patients (nine arteries, 7.2%), vasospasm could not be detected by MRA. Sequential changes in vasospasm could be well evaluated by MRA. CONCLUSION: MRA could be useful for management of cerebral vasospasm, although it cannot become a practical alternative to conventional angiography.

Adult↗

PubMed1997

Risks associated with cesarean sections in women with placenta previa.

OBJECTIVE: To investigate the risks associated with cesarean section performed because of placenta previa. METHODS: We retrospectively reviewed the records of 88 women with singleton pregnancies complicated by placenta previa who underwent cesarean sections and those of 176 (control) women with singleton pregnancies who required cesarean section because of complications other than placenta previa. RESULTS: The duration of gestation was 35.3 +/- 3.6 weeks for subjects with placenta previa and 36.9 +/- 3.8 weeks for the control subjects. The mean birth weight was 2,650 g +/- 75 g for infants of women with placenta previa and 2,644 g +/- 38 g for infants of the control subjects. Blood loss during surgery was greater for women with placenta previa than for the control subjects (1,154 ml +/- 924 ml vs 632 ml +/- 357 ml, p < 0.001). Blood transfusion was required in 13 of 88 (15%) women with placenta previa, compared with 4 of 176 (2.3%) of the control subjects (p < 0.001). An emergency cesarean hysterectomy was performed on 4 of the 88 (4.5%) women with placenta previa, and in none of the control subjects (p < 0.05). The Apgar score was < or = 7 at 5 minutes in 17 infants of the 88 (22%) women with placenta previa, compared with 17 infants of the 176 (11%) control subjects among infants born at > or = 33 weeks' gestation (p < 0.05); among infants with a birth weight > or = 2,000 g, the corresponding numbers were 15 (21%) and 13 (9.2%), respectively (p < 0.05). CONCLUSIONS: Cesarean section in the women with placenta previa was associated with increased blood loss, resulting in a blood transfusion rate 6.5 times higher than in the control subjects. These findings suggest that placenta previa might adversely affect the neonatal outcome.

Adult↗

PubMed1997

Acquired immune thrombocytopenia caused by IgG antiglycoprotein Ib antibody in a patient with Hodgkin's disease.

We studied a patient with thrombocytopenia associated with Hodgkin's disease (HD). The megakaryocyte number in the bone marrow and the level of platelet-associated IgG were both increased in the patient. Intravenous gamma-globulin therapy and chemotherapy for HD dramatically normalized the platelet count, suggesting that antibody produced by lymphoma cells is likely to account for the thrombocytopenia. Antigen-captured ELISA and Western blotting showed that the patient's serum had an IgG autoantibody against platelet membrane glycoprotein Ib. The patient's plasma had no inhibitory effect on normal platelet aggregation induced by ristocetin. These findings suggest that the autoantibody found in the patient had a pathogenetic role in the thrombocytopenia, but not in platelet dysfunction.

Adolescent↗

PubMed1997

Identification of surface molecules on eosinophils and lymphocytes in blood from patients with eosinophilia.

Surface molecules on eosinophils and lymphocytes in blood from patients with hypereosinophilic syndrome (HES), Kimura's disease and normal volunteers were examined. In all 3 patients with HES, CD54-positive eosinophils were increased and in some patients with HES and Kimura's disease HLA-DR-positive eosinophils were increased. Additionally, CD11b-positive, CD16-positive, CD25-positive, CD54-positive, CD69-positive and HLA-DR-positive lymphocytes were increased in some of these patients.

Angiolymphoid Hyperplasia with Eosinophilia↗

PubMed1997

Elevation of the serum uric acid level preceding the clinical manifestation of preeclampsia in twin pregnancies.

To assess changes in the serum uric acid level in the third trimester of twin pregnancies, a total of 152 consecutive women with twin pregnancies were examined. Serum uric acid levels were analyzed in the women at varying gestational weeks in the presence or absence of preeclampsia. A receiver operating characteristic curve was used to determine the optimal cutoff value of serum uric acid between 30 and 31 weeks of gestation predicting subsequent development of preeclampsia. Forty-four women (29%) developed preeclampsia (preeclampsia group) at 33.2 +/- 1.9 weeks (mean +/- SD) and gave birth at 35.4 +/- 1.5 weeks of gestation. The remaining 108 women (71%) gave birth at 35.6 +/- 1.7 weeks of gestation (control group without preeclampsia). Serum uric acid levels rose gradually with advancing gestation in both groups. In the preeclampsia group, they were already increased at 30-31 weeks of gestation and corresponded to those seen in the control group at 37 weeks. The cutoff value at 30-31 weeks was 5.5 mg/dl, with a sensitivity of 73% and a specificity of 74%. These results suggest that an elevation in serum urate preceded the onset of preeclampsia. Determination of the serum level of uric acid between 30 and 31 weeks of gestation was useful for detecting a higher risk of late-onset preeclampsia in twin pregnancies.

Cohort Studies↗

PubMed1997

Effect of beta 2glycoprotein I and human monoclonal anticardiolipin antibody on the protein S/C4b-binding protein system.

The effect of beta 2glycoprotein I (beta 2GPI) and human monoclonal anticardiolipin antibody (aCL) on the protein S/C4b-binding protein (C4BP) system was evaluated. The binding of C4BP to protein S was assessed by ELISA in the presence of beta 2GPI with/without human monoclonal aCL. beta 2GPI downregulated the binding between S and C4BP significantly. Human monoclonal aCL abolished the beta 2GPI inhibitory effect in a calcium (Ca++) independent fashion. In separate experiments, the reactivity of aCL towards protein S in the presence or absence of beta 2GPI and cardiolipin was investigated. Monoclonal aCL bound to protein S only in the presence of a combination of beta 2GPI and cardiolipin. This binding was Ca++ dependent. These findings suggest that human monoclonal aCL increases the affinity of C4BP for protein S, and that protein S may represent one of the targets for aCL when combined with beta 2GPI and cardiolipin. Both issues may explain acquired free protein S deficiency and the attendant risk of thrombosis in patients with aCL.

Animals↗

PubMed1997

Lupus erythematosus profundus around the salivary glands: a case resembling submandibular salivary gland disease.

In a 29 year old Japanese woman with SLE, a bilateral submandibular mass was detected. Computed tomographic (CT) scan suggested inflammatory changes around the submandibular glands. Histological findings of the deep skin biopsy showed typical changes of lupus erythematosus profundus (LEP). LEP should be considered in the differential diagnosis of an unexplained submandibular mass in a subject with SLE.

Adult↗