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Biomedical subjects

K Fujiwara

Publications and source records attributed to K Fujiwara.

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

Dimerization of small GTPase Rab5.

Rab proteins are small GTPases, localized to distinct cellular compartments, regulating specific steps of intracellular membrane trafficking. One member of the Rab family, Rab5, consists of three isoforms, Rab5a, Rab5b, and Rab5c, which have been shown to play an important role in early events of endocytosis. Using the yeast two-hybrid system, we have identified several cytosolic proteins that interact with the Rab5b Q79L (decreasing intrinsic and GTPase-activating protein-stimulated GTPase activities). Surprisingly, most positive clones were Rab5b or Rab5c, indicating that Rab5 could dimerize among extra-isoforms in the yeast two-hybrid system. In vitro and in vivo chemical cross-linking assays demonstrated that lipid-unmodified wild-type Rab5b purified from Escherichia coli, wild-type Rab5b, or a dominant active form Rab5b Q79L expressed in human 293T cells dimerized. Furthermore, the same assays using a Rab5b R81A substitution mutant showed that the Arg81 in the Switch II region [the second GTP/GDP binding motif (residues 74-93)] was essential for Rab5b dimerization. These results suggest that Rab5 isoforms can be dimerized depending upon the GTP-bound conformation, but independent upon a lipid modification.

Amino Acid Sequence↗
PubMed2001

[Evaluation of RI scintiscanning to parotid gland tumors].

We retrospectively evaluated preoperative radioisotope (RI) scintiscans in 275 patients (283 glands) with parotid tumors who undergoing surgery between 1987 and 2000. Technetium-99m-pertechnetate (Tc) scintigraphy was conducted on 201 glands. Oncocytoma and Warthin's tumor showed a high positive rate. In evaluating Warthin's tumor with Tc scintigraphy, sensitivity was 75% and specificity 88%; above the age of 40 years, specificity exceeded 90%. Gallium-67-citrate (Ga) scintigraphy was conducted on 207 glands. Malignant parotid tumors showed high positivity (85%), but the specificity of positive findings was quite low (38%) because 44% of benign pleomorphic adenoma, which occupied major material, showed Ga-positive findings. Ga-negative findings indicated high probability (95%) of benign tumors. Thus, Tc scintigraphy is effective in diagnosing Warthin's tumor, while Ga scintigraphy is effective in diagnosing benign tumors.

Adenolymphoma↗
PubMed2001

[Continuous intrathecal administration of nicardipine using a portable infusion pump system for management of vasospasm after subarachnoid hemorrhage].

We studied the feasibility of intrathecal nicardipine administration using a portable infusion pump system in five cases (two males and three females) of subarachnoid hemorrhage (SAH). All of the five cases manifested severe SAH of Hunt & Kosnic grade 3 or 4, and Fisher CT group 3. Aneurysmal sites of five cases were as follows: three internal carotid-posterior communicating artery (IC-PC) aneurysms and two anterior communicating artery (Acom) aneurysms. The container of the infusion pump system was filled with 105 ml of nicardipine-saline solution (2:1), and this system was connected to the cisternal tube. The solution was continuously injected at a daily dose of 12 ml (8 mg of nicardipine). This therapy was continued for 14 days, and new nicardipine solution was supplied only once at 8 days after the operation during this therapy. No postural restraint of patients was necessary, even during physical movement for rehabilitation. Postoperative angiography was performed in three of five cases at one week after the operation. No angiographic vasospasm was observed in any of the three cases. Symptomatic vasospasm was observed in one case of right IC-PC aneurysm as a transient total aphasia and right hemiplegia, which recovered within several hours due to induced hypervolemia and hypertension therapy. Mild meningitis at 14 days after the operation complicated this treatment in one case, but it improved in a few days after the cisternal tube was removed. It was speculated that meningitis was caused by cerebrospinal fluid leakage from the scalp exit site of the cisternal tube. All of the five cases had obtained good recovery at three months after the operation. These results show that, although this method involves a risk of infection, it has the advantage of easiness and convenience over conventional methods. Though further improvement of this method is required, this preliminary stage is potentially useful for delivering not only nicardipine, but also for other drugs which may be used in intrathecal administration therapy.

Aged↗
PubMed2001

[Two cases of acute eosinophilic pneumonia--analyses of cytokines in BALF before and after treatment].

Acute eosinophilic pneumonia (AEP) has been well recognized as sudden onset respiratory failure characterized by an increased eosinophilic cell count in the bronchoalveolar lavage fluid (BALF). Although several lines of research have demonstrated that the Th2 cytokine network is likely to play a pivotal role in the development of AEP, that mechanism has not been clearly understood yet. Previous reports published in Japan demonstrated that the BALF CD4/CD8 ratio in patients with AEP ranged between 1.1 and 5.8. In this report, we describe 2 cases of AEP in which the CD4/CD8 ratios were 0.3 and 7.8 when present. We measured IL-4, IL-5, IL-10 and IFN gamma in the BALF before and after treatment in these patients. IL-5 decreased drastically after the treatment phase, while the other cytokines did not change much. We concluded that the IL-5 concentration in the BALF is probably related to the development of AEP. In addition, we also speculated that the CD4/CD8 ratio in BALF from patients with AEP may be affected whether a patient has an atopic background or not.

Acute Disease↗
PubMed2001

[Pure red cell aplasia developing during the course of primary macroglobulinemia associated with pseudochylothorax and IgA nephropathy].

A 74-year-old man who had undergone artificial pneumothorax therapy for pulmonary tuberculosis 40 years earlier was admitted because of blurred vision, headache, and numbness of the lower limbs in October 1997. He presented with anemia and leukocytopenia with monoclonal gammopathy of IgM (kappa). His bone marrow was diffusely infiltrated with small lymphocytes, plasmacytoid lymphocytes, and plasma cells expressing IgM, kappa surface immunoglobulin. On the basis of these findings, primary macroglobulinemia (PMG) was diagnosed. CT scan of the chest demonstrated pleural effusion of the right lung encapsulated in a thickened pleura, and pseudochylothorax was diagnosed from a specimen of chyliform fluid which contained numerous cholesterol crystals and was positive for Mycobacterium tuberculosis (MT) on PCR assay. The patient's condition was also complicated by chronic renal failure due to IgA nephropathy, which may have been a consequence of the tuberculosis, possibly due to an abnormal IgA-mediated immune response to MT. The patient gradually developed pure red cell aplasia during the course, probably due to an autoimmune mechanism. Later in the course, immunoglobulin gene analysis of the malignant cells of PMG showed that they were derived from antigenically selected cells. In the context of antigenic stimulation, the role of MT antigen in the pathogenesis of PMG was of interest in this patient.

Aged↗
PubMed2001

[Disseminated bone marrow metastases from gastric cancer: detection and monitoring the effectiveness of chemotherapy by bone marrow scintigraphy].

Disseminated bone marrow metastasis of cancer is a critical condition, frequently complicated by disseminated intravascular coagulation (DIC). A 32-year-old man with gastric cancer was diagnosed as having disseminated bone marrow metastases. Bone scintigraphy demonstrated many abnormal radionuclide accumulations in the whole body. Bone marrow aspiration revealed cancer cells. Bone marrow scintigraphy with 111In-Cl3 demonstrated central marrow failure and peripheral expansion. The remission of DIC was observed after sequential methotrexate and 5-FU therapy, then uptake of radionuclide in the central bone marrow was remarkably improved by bone marrow scan. After thirteen anti-cancer chemotherapies, recurrence of DIC was suspected because of the reduction of blood platelet count. Nevertheless, repeated bone marrow scan still demonstrated the central bone marrow clearly. The patient discharged from our hospital without the recurrence of DIC. We considered bone marrow scintigraphy is useful in the detection of disseminated bone marrow metastases of cancer and monitoring the effectiveness of chemotherapy.

Adult↗
PubMed2001

[Current status of adjuvant endocrine therapy for hormone responsive breast cancer].

Three important meetings on adjuvant hormone therapy for breast cancer were held recently: the 5th EBCTCG Meeting, NIH Consensus Meeting, 7th International Conference on Adjuvant Therapy of Primary Breast Cancer. The conclusions of these meetings are: 1. adjuvant hormone therapy should be indicated only for patients with estrogen/progesterone receptor positive cancer, 2. five years of tamoxifen is the standard care at present, 3. ovarian ablation by any means has been proved effective in premenopausal patients and LH-RH agonist should be given at least two years, and 4. aromatase inhibitors should not be used in clinical practice, because several prospective randomized trials are ongoing at present. The patients treated with LH-RH agonist combined with tamoxifen showed better relapse-free survival compared with LH-RH agonist alone in the INT-0101 trial. This was an important trial because combined hormone therapy had not been proven more effective than individual hormone therapy previously. Combined hormone therapy including LH-RH agonist may be considered in premenopausal patients. There is a growing consensus that chemotherapy is effective through the ovarian suppression. In this sense, hormonal therapy should be considered first for hormone responsive patients. On the contrary, standard chemotherapy has shifted from CMF combination to an anthracycline containing regimen. Chemoendocrine therapy may be considered in high risk patients.

Antineoplastic Agents, Hormonal↗
PubMed2001

[Three cases of pulmonary eosinophilic granuloma].

CASE 1. A 55-year-old man was admitted because of an abnormality in chest radiographs. Chest HRCT showed multiple cystic lesions with thick and thin walls, and nodules; and strongly suggested pulmonary eosinophilic granuloma (EG). Open lung biopsy revealed granuloma formation and a fibrotic area consistent with EG. CASE 2. A 28-year-old woman was admitted because of chest pain and dyspnea. Chest radiography revealed bilateral pneumothorax. Chest HRCT showed multiple cystic lesions with thick walls involving the entire lung. As lung biopsy revealed, proliferative lesions and cavitation containing S-100 protein-positive histiocytes, we diagnosed this case as pulmonary EG in the active stage. CASE 3. A 32-year-old woman was admitted because of dyspnea. Chest CT showed bullous changes in the lung. As an open lung biopsy revealed, honeycomb changes with S-100 protein-positive histiocytes, this case was diagnosed as the regressive phase of EG. It is known that the chest radiography and HRCT findings of EG are characteristic and vary with the stage, so a surgical lung biopsy is necessary for diagnosis of EG. It is considered that the prognosis of the active phase of EG involving the entire lung is poor.

Adult↗
PubMed2001

Preassignment examination for personnel on Iwo Jima.

The Japan Maritime Self-Defense Force (JMSDF) requires all personnel assigned to Iwo Jima to undergo a preassignment medical examination. The efficacy and benefit of this mandatory examination has not been evaluated objectively in depth. Our purpose was to review the health status of JMSDF personnel assigned to Iwo Jima and to evaluate the correlation of the preassignment medical examination to their current health status for the study period. We divided the participants into two groups. Group Y was composed of JMSDF personnel receiving a preassignment medical examination, and group N was composed of those personnel who did not receive the examination. After the annual health examination, health status was evaluated using objective criteria. We found little statistically significant difference among group Y and group N participants. However, proportionally more patients currently receiving care for or diagnosed with hypertension, hyperuricemia, or severe obesity were identified as being members of group N than group Y. We have demonstrated that the preassignment medical examination may contribute to predicting the health status of potential Iwo Jima personnel and may contribute to controlling the cost of care associated with these specific diagnoses by limiting the assignment of at-risk personnel.

Adult↗
PubMed2001

[Staged operation for right isomerism with total anomalous pulmonary venous return: report of a case].

A male infant with right isomerism, single ventricle, severe pulmonary stenosis (PS), and total anomalous pulmonary venous return (TAPVR) underwent successful staged Fontan operation. Pulmonary vein drained into right superior vena cava without a stenotic lesion. Common pulmonary venous chamber was also connected with the atrium by a thin bridging vein. Blalock-Taussig shunt was performed at 2-month-old. Because of progressive pulmonary congestion, an anastomosis between common pulmonary venous chamber and the atrium followed 4 days after the first shunt. Bidirectional cavopulmonary shunt was performed 7 months after the second operation. Because of progressive atrioventricular valve regurgitation, repeated bandings of the shunt were required to regulate the pulmonary flow. Total cavopulmonary connection was completed 9 months after the BCPS. Staged operation is a useful strategy to acquire an appropriate pulmonary blood flow for the isomeric heart with TAPVR and severe PS.

Cardiac Surgical Procedures↗
PubMed2001

Grafting of encapsulated genetically modified cells secreting GDNF into the striatum of parkinsonian model rats.

In order to deliver glial cell line-derived neurotrophic factor (GDNF) into the brain, we have established a cell line that produces GDNF in a continuous fashion by genetic engineering. These cells were encapsulated and grafted into parkinsonian model rats that had received unilateral intrastriatal injection of 6-hydroxydopamine 2 weeks earlier. Neurochemical analysis showed that GDNF has been produced from the capsule for 6 months after grafting and histological analysis revealed good survival of GDNF-producing cells in the capsule 6 months after grafting. The density of nigrostriatal dopaminergic fibers in the striatum as well as the number of dopaminergic cell bodies in the substantia nigra recovered significantly after GDNF-producing cell grafting. These results suggest the possible application of GDNF-producing cell grafting for the treatment of Parkinson's disease.

Animals↗
PubMed2001

Neurotrophic factor-secreting cell grafting for cerebral ischemia: preliminary report.

In this experiment, we examined a possible protective effect of encapsulated neurotrophic factor-secreting cell grafting for ischemic injury. We established a basic fibroblast growth factor (bFGF)-secreting cell line by genetic manipulation. We enveloped these cells into polymer capsules, which consist of a semipermeable membrane, and implanted them into the right striatum of rats. At 6 days after implantation, these rats received right middle cerebral artery occlusion (MCAO) using interluminal suture technique. At 24 h after MCAO, rats were sacrificed and their cerebral infarction volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining and image analysis. We found approximately 30% reduction in infarct volume in the encapsulated bFGF-secreting cell grafting groups vs. the encapsulated naive BHK cell grafting group or the without implantation group. We measured bFGF secretion from encapsulated bFGF-secreting cells using enzyme-linked immunosorbent assay (ELISA). The retrieved capsules continued to secrete bFGF. There was no significant difference of bFGF secretion between the capsules before and after transplantation. A large number of viable BHK-bFGF cells was observed within the full length of the retrieved capsule. These results indicate that encapsulated bFGF-secreting cell grafting exerts a protective effect on ischemic injury.

Animals↗
PubMed2001

Actual invasive potential of human hepatocellular carcinoma revealed by in situ gelatin zymography.

BACKGROUND: The matrix-degrading proteinases are believed to play an important role in the invasion and metastasis of hepatocellular carcinoma (HCC), but no one has ever seen the in situ matrix-degrading activity in HCCs. PURPOSE: To demonstrate the cellular localization of actual gelatinolytic activity and to investigate the invasive potential of human HCC. EXPERIMENTAL DESIGN: HCC cases (30) were subjected to in situ gelatin zymography and SDS-gelatin gel zymogram. RESULTS: In situ gelatin zymography revealed a heterogeneous gelatinolytic activity in HCC cells, as well as stromal cells of noncancerous livers. The gelatinolytic intensity was stronger in 15 HCC nodules than in the corresponding noncancerous livers and was significantly associated with the cancer invasion to the capsule of the HCCs and to the portal veins. An intense gelatinolytic activity was detected in HCC cells in the front of tumor invasion. SDS-gelatin gel zymogram revealed gelatinases A and B that were mostly in latent forms. CONCLUSIONS: The present study demonstrates high gelatinolytic activity at the invasive front of HCCs at a cellular level and that HCC has an invasive potential with the gelatin (matrix)-degrading metalloproteinases. Furthermore, it suggests the importance of the activation mechanism of gelatinolytic enzymes in the invasion and metastasis of HCCs.

Carcinoma, Hepatocellular↗
PubMed2001

[Double switch operation (Senning and Rastelli operation) with left atrial augumentation by in situ autologous pericardium: a case report].

A 23-month-old female infant with situs solitus, atrioventricular and ventriculoarterial discordance, pulmonary atresia, ventricular septal defect, who had received modfied right Blalock-Taussig shunt (4 mm Gore-Tex tube) at the age of 2 months, was carried out double switch operation with left atrial augumentation by in situ autologous pericardium. The spatial position of the heart was mesocardia. The systemic right ventricular end-diastolic volume was 100% of normal, and the pulmonic left ventricular end-diastolic volume was 105% of normal. Atrioventricular valvular regurgitation was not found. Postoperative course was uneventful. On the 28th postoperative day,she discharged from hospital. The disadvantage of double switch operation is difficulty of atrial switch procedure, because most patients have a small atrium due to dextrocardia or mesocardia. For the purpose of atrial augumentation without artificial materials, our modified Senning procedure is useful. But longer follow-up is necessary to determine whether this technique is indeed beneficial.

Aorta↗
PubMed2000

Relationship between the configurations of 2-phenyltetrahydrothiophenium 1-methylides and their rearrangement products

trans-2-Phenyltetrahydrothiophenium 1-methylide (trans-3), which is generated by fluoride ion-induced desilylation of trans-2-phenyl-1-[(trimethylsilyl)methyl]tetrahydrothiophenium salt (trans-2), gave a mixture of 1,4,5,10a-tetrahydro-3H-2-benzothiocine (4) ([2,3]sigmatropic rearrangement product) and 4-methylsulfanyl-1-phenyl-1-butene (5) (Hofmann elimination product). Ylide trans-3 cannot undergo [2,3]sigmatropic rearrangement because the ylide-carbon is too far from the phenyl group, and trans-3 would instead isomerize to cis-3. In this paper, we discuss the mechanism of the isomerization of trans-3 to cis-3.

Journal Article↗
PubMed2000

Lysophosphatidic acid enhances collagen gel contraction by hepatic stellate cells: association with rho-kinase.

We studied the effect of lysophosphatidic acid (LPA) on collagen gel contraction by cultured rat hepatic stellate cells (HSCs) in association with the function of Rho-kinase, one of the target molecules of small GTPase Rho. Binding studies showed a single class-binding site of LPA on HSCs. LPA enhanced the contraction of a collagen lattice seeded with HSCs. LPA increased the number of HSCs with polygonal morphology that contained actin stress fibers, and enhanced the phosphorylation of myosin light chain and the assembly of focal adhesion kinase and RhoA around fibronectin-coated beads seeded on HSCs. The electric cell-substrate impedance sensor system showed that LPA enhanced adhesion of HSC to extracellular substrate. All the effects of LPA were suppressed by Y-27632, Rho-kinase inhibitor. These data support the notion that LPA is involved in modulating HSC morphology, its attachment to surrounding extracellular matrix and its contraction by a mechanism involving Rho-kinase.

Actins↗
PubMed2000

On the tryptophan residue of smooth muscle myosin that responds to binding of nucleotide.

Initially, we asked which (of 10) smooth muscle myosin head residues responds to MgADP or MgATP binding with enhanced fluorescence emission (Trp-441 and Trp-512 were leading candidates)? To decide, we prepared sham-mutated smooth muscle heavy meromyosin (HMM), W441F HMM, and W512F HMM. On adding MgATP, emission of wild-type and W441F HMMs increased by 25-27%, but that of W512F HMM by 5%. So, in myosin, 512 is the "sensitive Trp." Unexpectedly, properties of W512F HMM [elevated Ca(2+)-ATPase, depressed EDTA (K(+))-ATPase, no regulation of its basal or actin-activated Mg(2+)-ATPase by phosphorylation of its "regulatory" light chain, limited actin activation, and inability to move actin filaments in a motility assay] are strikingly like those of smooth muscle myosin reacted at Cys-717 with thiol reagent. From crystallography-based [Houdusse, A., Kalabakis, V. N., Himmel, D., Szent-Györgyi, A. G. & Cohen, C. (1999) Cell 97, 459-470] simulations, we found that in wild-type HMM with MgADP added, Trp-512 is in a "hydrophobic pocket," but that pocket becomes distorted in W512F HMM. We think that there is a "path of influence" from 512 to 717 to the active site. We suggest that the mutational changes at 512 are transmitted along this path to Cys-717, where they induce changes similar to those caused by reacting wild-type HMM with thiol reagent.

Adenosine Diphosphate↗