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Biomedical subjects

R Tanaka

Publications and source records attributed to R Tanaka.

At least 325 records · Page 18Linked to original sources
PubMed1996

Targeting chemotherapy for malignant brain tumor using thermosensitive liposome and localized hyperthermia.

Thermosensitive liposomes are microscopic vesicles that can contain drugs and release them effectively in response to hyperthermia. To deliver an antitumor drug specifically to brain tumor, the authors used thermosensitive liposomes containing cis-diamminedichloroplatinum (CDDP) in conjunction with localized brain heating. The authors then investigated the antitumor effect on rat malignant glioma. Rous sarcoma virus-induced malignant glioma cells were transplanted into the brains of Fisher rats. Ten days after tumor inoculation, the rats were assigned to one of six treatment groups: control, free CDDP, hyperthermia, free CDDP + hyperthermia, liposomes containing CDDP (CDDP-liposome), and CDDP-liposome + hyperthermia. Liposomes containing CDDP or free CDDP were injected via the tail vein. Brain tumor heating was administered by means of a radiofrequency antenna designed at our institute. The rats treated with CDDP-liposome + hyperthermia had the longest survival time and the tumor CDDP level of this group was the highest when compared to the other groups. Histopathological examination showed that tumor cells were necrotized but surrounding normal brain tissue remained undamaged. On the basis of these findings we suggest that the combination of thermosensitive liposome and localized hyperthermia may better focus antitumor drugs to the tumor, providing a significantly greater antitumor effect.

Animals↗
PubMed1996

Induction of vascular permeability enhancement by human tryptase: dependence on activation of prekallikrein and direct release of bradykinin from kininogens.

Tryptase is a trypsin-type serine protease that is released from mast cells. Bradykinin (BK) is released directly from kininogens or through activation of either Hageman factor or subsequent plasma prekallikrein. Its nasal administration or inhalation induces allergy-like symptoms. Although elevated levels of tryptase and BK in allergic fluids have been detected, the role of this proteinase and the mechanism of BK production at allergic reaction sites are still unknown. To investigate the pathologic functions of tryptase, the enzyme, purified from human lung, was incubated with normal human plasma, deficient plasmas, kininogens, or prekallikrein. High molecular weight kininogen was then added, and the mixtures were examined for vascular permeability enhancement (VPE) activity, a representative function of bradykinin, using guinea pig skin. Tryptase-treated plasma induced VPE in a dose-dependent manner; activity was lost in the absence of a kininase inhibitor but not an antihistamine drug. Tryptase produced VPE activity from normal or Hageman factor-deficient plasma, but only 30% of this activity was produced from prekallikrein-deficient plasma. Significantly, no activity was obtained from kininogen-deficient plasma. Deficient plasma that were reconstituted with each missing factor resulted in VPE-inducing capacity by tryptase, equivalent to that found with normal plasma. Incubation of tryptase with high or low molecular weight kininogen induced VPE activity in a dose- and incubation time-dependent manner. Prekallikrein incubated with tryptase also generated a soybean trypsin inhibitor-sensitive VPE-inducing activity from high molecular weight kininogen. The loss of tryptase VPE-producing activity as a function of incubation time was found to be a result of spontaneous inactivation of the enzyme and not of the degradation of high molecular weight kininogen by the enzyme. We conclude that tryptase induces VPE by releasing BK, primarily through prekallikrein activation, but also through direct release from kininogens. This indicates that this mast cell-derived proteinase contributes to kinin production in allergic diseases.

Animals↗
PubMed1996

[Tracheal carcinoma causing severe tracheal stenosis].

A 47-year-old woman was admitted to our hospital because of shortness of breath. She had wheezed for a long time before admission. A flow-volume curve showed a pattern consistent with a fixed obstruction of the trachea. CT findings also revealed severe stenosis of the trachea caused by a tumor mass. Tracheal carcinoma was diagnosed after transbronchoscopic biopsy. The patient received chemotherapy and radiation therapy concurrently for about six weeks. Her symptoms resolved, and a second flow-volume curve had a normal pattern. Tracheal carcinoma should be included in the differential diagnosis of airway obstruction. In such cases, the flow-volume curve can be useful as a screening test.

Adenocarcinoma↗
PubMed1996

Rhabdomyolysis following administration of cyclophosphamide: a case report in a BMT recipient.

Massive rhabdomyolysis followed by myocardial necrosis was observed in a 14-year-old patient undergoing allogeneic bone marrow transplantation for severe aplastic anemia. Rhabdomyolysis was preceded by the administration of cyclophosphamide as part of a preparative regimen for transplantation Although the specific etiology of this rhabdomyolysis is still unknown, an association with high-dose cyclophosphamide should be noted.

Bone Marrow Transplantation↗
PubMed1996

[Standardization of use of 4-F size catheter for selective transcatheter angiography and intervention of abdomen].

To evaluate the safety and efficacy of a new 4 French (F) catheter/sheath system with large lumina for selective abdominal arteriography and intervention, the usefulness of the 4F sheath (4F group, 88 patients) was compared with that of a 5.5F sheath and a 7F sheath (5.5F group, 7F group, 156 patients). The compression time of the arterial puncture site and the ambulation time in the 4F group were significantly shorter than those in the 5.5F and 7F groups. The hemorrhagic complication rate in the 4F group (15%) was less than those in the 5.5F group (23%) and 7F group (27%). The severity of hemorrhagic complications in the 4F group (hematoma 2.3%, woozing 14%, and rhexis 0%) was significantly less than in the 5F group (3%, 21%, 0%) and 7F group (11%, 19%, 2.4%). The controlability of the 4F catheter as compared with a 5F catheter was estimated in 35 patients by questionnaire. The torque transmissibility and the endurability of the kink of the 4F catheter were poor in comparison with the 5F catheter. However, with respect to the ability to follow over a guidewire, the 4F catheter showed great advantage over the 5F catheter. It is concluded that the 4F catheter/sheath system is feasible for general use in selective abdominal arteriography and interventions.

Abdomen↗
PubMed1996

Complete recanalization via fibrinolytic therapy can reduce the number of ischemic territories that progress to infarction.

PURPOSE: To clarify the clinical significance of fibrinolytic therapy for acute ischemic stroke. METHODS: We analyzed findings in 18 patients with occlusion of a major artery in respect to cerebral blood flow thresholds for infarction. Nine of these patients had shown complete recanalization just after the treatment, between 3.5 and 7.25 hours after symptom onset, and the other nine had shown no change. Cerebral blood flow was measured by single-photon emission CT using 99mTC-labeled hemamethylpropyleneamine oxime and assessed semiquantitatively: multiple regions of interest were placed on the section images and two parameters, the R/CL ratio and the R/CE ratio, were calculated (where R represents a mean count of the region of interest in the affected hemisphere, CL on the opposite side, and CE in the cerebellar hemisphere on the affected ischemic side). RESULTS: Reperfusion significantly reduced the development of infarction in the regions of interest with an R/CL ratio between 0.65 and 0.85 or an R/CE ratio between 0.55 and 0.75. No correlation was observed between the development of infarction and the duration of ischemia. The cerebral blood flow threshold in patients without recanalization was higher than that in patients with recanalization. CONCLUSION: Reperfusion achieved by fibrinolytic therapy in the acute stage can save ischemic brain within a limited cerebral blood flow value.

Aged↗
PubMed1996

[5-lipoxygenase inhibitors in asthma therapy].

Leukotrienes are biological active lipids produced from arachidonic acid in cell membrane by the enzyme 5-lipoxygenase. During anaphylaxis, large amounts of leukotrienes are generated in the lungs, causing bronchoconstriction. Leukotrienes exacerbate asthma in different ways including cellular infiltration, chemotaxis aggregation, and degranulation (LTB4), as well as airway constriction, vasopermeability, mucous hypersecretion, mucosal edema and reduced mucociliary clearance (LTC4, LTD4 and LTE4). It is expected that 5-lipoxygenase inhibitors are effective in bronchial asthma by blocking leukotriene synthesis, and its indication is chronic therapy to prevent symptoms of bronchospasm. Zileuton is the 5-lipoxygenase inhibitor most advanced in clinical development. As bronchial asthma is thought to be provoked by a variety of causes, therapeutic drug should be selected according to the state of the disease.

Arachidonate 5-Lipoxygenase↗
PubMed1995

Partial inhibition of protein synthesis accelerates the synthesis of porphyrin in heme-deficient mutants of Escherichia coli.

Mutants of Escherichia coli defective in the HemA protein grow extremely poorly as the result of heme deficiency. A novel hemA mutant was identified whose rate of growth was dramatically enhanced by addition to the medium of low concentrations of translational inhibitors, such as chloramphenicol and tetracycline. This mutant (H110) carries mutation at position 314 in the hemA gene, which resulted in diminished activity of the encoded protein. Restoration of growth of H110 upon addition of the drugs mentioned above was due to activation of the synthesis of porphyrin. However, this activation was not characteristic exclusively of cells with this mutant hemA gene since it was also observed in a heme-deficient strain bearing the wild-type hemA gene. The activation did not depend on the promoter activity of the hemA gene, as indicated by studies with fusion genes. It appears that partial inhibition of protein synthesis via inhibition of peptidyltransferase can promote the synthesis of porphyrin by providing an increased supply of glutamyl-tRNA for porphyrin synthesis. Glutamyl-tRNA is the common substrate for peptidyltransferase and HemA.

Aldehyde Oxidoreductases↗
PubMed1995

Decision Making Using Postoperative CEA and CA 15-3 for Detection of Breast Cancer Recurrence.

To determine the clinical implications of postoperative levels of serum carcinoembryonic antigen (CEA) and CA 15-3 as follow-up parameters for breast cancer, a retrospective study was conducted on 157 patients who underwent curative surgery for breast cancer. Twenty-three patients had recurrences and 134 patients were without recurrence for more than one year after measuring the tumor marker. The receiver operating characteristic (ROC) curves indicated that CA 15-3 performed more accurately than CEA in discriminating between patients with recurrence (n = 23) and those without (n = 134). Of 23 patients with recurrence, CEA was elevated above the normal range (<2.9 ng/ml) in 32% and CA 15-3 was elevated above the normal range (> 20U/ml) in 67%. The elevation of the markers preceded the clinical appearance of metastases in 2 patients for CEA and in 5 patients for CA 15-3. False positive rates for CEA and CA 15-3 in the 134 patients without recurrence were 4% and 10%, respectively. Nevertheless, these rated became 0% when the cut-off values were doubled. When the postoperative serum level of either CEA or CA 15-3 exceeds twice the upper limit of the normal range or when, in patients with unfavourable prognostic characteristics (node positive or large tumor), either of these values is between the upper limit of the normal range and double the value, recurrent breast cancer must be assumed. For such patients, further investigations with high-sensitivity radiographic modalities are warranted because early treatment may be able to provide survival benefit.

Journal Article↗
PubMed1995

Accelerated cell-cycling of hematopoietic progenitor cells by growth factors.

Recent advances in molecular biology have led to the identification of hematopoietic growth factors that support and influence the proliferation of hematopoietic progenitor cells in vitro and in vivo. Although these factors have been extensively studied, little is known of their role in the regulation of cell-cycling of hematopoietic progenitors, especially in the early stage of hematopoiesis. In the present study, we examined the effects of early acting growth factors on proliferative kinetics of hematopoietic progenitors by monitoring the number of cells in individual developing colonies, using an in vitro clonal assay. Interleukin-11 (IL-11) or steel factor (SF), alone or in combination, shortened the time for the size of IL-3-dependent colonies to double. Consecutive replating experiments provided evidence for direct action of growth factors on the growth rate of hematopoietic progenitor cells. Shortening of the time for the total cell number in the colonies to double was due to a reduction in time for each single cell within the respective colonies to become two daughter cells, and there was no alteration in the incidence of cells with a proliferative capacity. Cell-cycle analysis demonstrated that IL-11 has the potential to induce a shortened time for cell-cycle of hematopoietic progenitor cells without affecting distribution of each fraction of the cell-cycle, whereas SF has the potential to reduce cell-cycle time mainly by decreasing the time required for hematopoietic progenitor cells to go through the G1 phase. These results suggest that growth factors may modulate cell-cycling of hematopoietic progenitor cells.

Animals↗
PubMed1995

Unbudded G2 as well as G1 arrest in the stationary phase of the basidiomycetous yeast Cryptococcus neoformans.

Stationary-phase cells of Cryptococcus neoformans displayed two morphological characteristics: virtually all the cells were unbudded even in the early stationary phase and even when grown in rich media, and average cell size increased from that of exponential-phase cells. DNA contents for small and large stationary-phase cells were determined by quantitative fluorescence microscopy after DNA staining with propidium iodide or DAPI. Small cells contained G1 DNA, whereas large unbudded cells had either a G2 or G1 DNA content, indicating that Cr. neoformans can enter into the stationary phase from either the G1 or G2 period.

Cryptococcus neoformans↗
PubMed1995

gp130 and c-Kit signalings synergize for ex vivo expansion of human primitive hemopoietic progenitor cells.

gp130, a signal-transducing receptor component of interleukin 6 (IL-6), associates with an IL-6 and IL-6 receptor (IL-6) complex and transduces signals. To examine the role of gp130 signaling in the expansion of human hemopoietic progenitor cells, we tested the effects of a recombinant soluble human IL-6 receptor (sIL-6R) and/or IL-6 in combination with other cytokines on purified human umbilical cord blood CD34+ cells, using methylcellulose clonal assay and suspension culture in the presence or absence of serum. A combination of sIL-6R and IL-6 (sIL-6R/IL-6), but not sIL-6R or IL-6 alone, was found to dramatically stimulate expansion of hemopoietic progenitor cells as well as CD34+ cells in the presence of stem cell factor. Significant generation of multipotential hemopoietic progenitors over a period of 3 weeks in suspension culture and efficient formation of colonies, especially multilineage and blast cell colonies, in methylcellulose assay supplemented with a combination of sIL-6R/IL-6 together with stem cell factor were observed in serum-containing and serum-free culture. Addition of anti-gp130 monoclonal antibodies or anti-IL-6R monoclonal antibodies to the above cultures dose-dependently inhibited the expansion of progenitor cells in suspension culture and also completely blocked the formation of multilineage colonies in methylcellulose culture. These findings demonstrated that the significant expansion of human primitive hemopoietic progenitors could be achieved with the gp130 and c-Kit signalings initiated by the sIL-6R/IL-6 complex in the presence of stem cell factor and suggested the possible application of this method for ex vivo expansion of CD34+ cells for bone marrow transplantation.

Antibodies, Monoclonal↗
PubMed1995

Model for the complex between protein G and an antibody Fc fragment in solution.

BACKGROUND: Streptococcal protein G and staphylococcal protein A are bacterial antibody-binding proteins, widely used as immunological tools, whose antibody-binding domains are structurally quite different. The binding of protein G to Fc fragments is competitive with respect to protein A, suggesting that the binding sites for protein A and protein G on Fc overlap, notwithstanding the fact that they lack sequence or structural similarity. RESULTS: To resolve this issue, the residues involved in the interaction between an IgG-binding domain of protein G (domain II) and the Fc fragment of mouse IgG2a have been identified by use of 13C and 15N NMR. Binding of protein G domain II selectively perturbed resonances from residues between the CH2 and CH3 domains of Fc, whereas in domain II the residues affected are primarily those on the alpha-helix and the third strand of the beta-sheet. This information was used, together with the structures of the two uncomplexed proteins, to construct a model of the complex, using Monte Carlo minimization techniques. In this model, the alpha-helix of protein G lies in the same position as helix 1 of protein A in the crystal structure of the protein A:Fc complex, but its orientation differs from the latter by 180 degrees. CONCLUSIONS: The interactions of the bacterial antibody-binding proteins with their 'target' immunoglobulins involve a very versatile set of protein-protein interactions. First, the IgG-binding domains of protein A and protein G have quite different three-dimensional structures, but bind to sites on the Fc fragment that overlap extensively. Secondly, protein G employs two quite different regions of its surface to bind to the Fab and Fc regions of IgG.

Antigens, Bacterial↗
PubMed1995

Prognostic value of proliferating cell nuclear antigen (PCNA) immunostaining in neuroblastoma.

Immunostaining for proliferating cell nuclear antigen (PCNA), a marker of cell proliferation, is being increasingly used to study the proliferative activity of tumors, and the PCNA labeling index has been correlated with the prognosis of several malignant neoplasms. Formalin-fixed, paraffin-embedded tissue specimens of 24 primary neuroblastomas were immunostained using an anti-PCNA monoclonal antibody and the PCNA index was calculated. Then the relationship between the PCNA index, prognosis, and various other factors was assessed, retrospectively. The mean PCNA index was 11.0%. Patients having tumors with a high PCNA index (> or = 11.0%) showed a significantly lower survival rate than those possessing tumors with a low PCNA index (P < 0.001). Moreover, the tumors showing N-myc amplification had a high mean PCNA index of 15.6%, while those without N-myc amplification had a low mean index of 1.7% (P < 0.01). The PCNA index was closely related to the prognosis of neuroblastoma and to N-myc amplification. It has the potential to be a useful prognostic indicator of the patients with neuroblastoma.

Child↗
PubMed1995

Dysembryoplastic neuroepithelial tumor: report of a case without typical glioneuronal elements.

We studied a temporal lobe lesion found in a 44-year-old woman with a 25-year history of intractable complex partial seizures. Histologically, the lesion contained several nodular areas differing in cellular composition within the disarranged uncal cortex; in each area, neuronal and small round cells, mature ganglion cells and fibrillary astrocytic cells predominated. Ultrastructurally, the small round cells demonstrated neuronal, astrocytic or oligodendrocytic features. The astrocytic cell processes were occasionally covered by basal laminae. The mature ganglion cells had well-developed rough endoplasmic reticulum, many mitochondria and lipofuscin granules in their cytoplasm. No dense-cored vesicles were evident. We diagnosed this temporal lobe lesion as a dysembryoplastic neuroepithelial tumor (DNT), although no areas of typical glioneuronal elements with mucinous matrix were evident. This case suggests that a glioneuronal element is not always a constant feature of DNT, and that although mature ganglion cell nodules may be present, they may differ from those of gangliocytomas and gangliogliomas in lacking intracytoplasmic dense-cored vesicles. The presence of occasional astrocytic cell processes covered by basal laminae strongly suggests that some of the constituent astrocytic cells were of subpial astrocytic origin.

Adult↗