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Biomedical subjects

Y Fujii

Publications and source records attributed to Y Fujii.

At least 433 records · Page 24Linked to original sources

[A case of complete mediastinal goiter located in the retrotracheal region: review on reported cases from 1986 to 1997 in Japan].

A 66-year-old man was admitted to our hospital as a result of an abnormal shadow which was observed on his chest X-ray. A chest CT scan and chest MRI revealed an upper mediastinal tumor. The tumor was located in the retrotracheal region and resected completely following a thoracotomy. Histological examination of the tumor revealed follicular adenoma of the thyroid gland. Complete mediastinal goiter is a relatively rare lesion, with only 59 cases (including our case) in Japan prior to 1997. Only two cases were reviewed, in which the tumors were located in the retrotracheal region, out of the 59 cases in Japan.

Adenoma↗

[A case of subarachnoid hemorrhage complaining of deafness].

A 64-year-old female came to our department because of a sudden onset of bilateral deafness 2 days before. She had sudden onset of mild headache, nausea and vomiting 9 days before, but was diagnosed as food poisoning by her home doctor. Her symptoms disappeared on the following day. Neurological examination revealed bilateral deafness, right facial palsy of central type and very slight neck stiffness. CT showed inconspicuous subarachnoid hemorrhage, but lumber puncture revealed definite subarachnoid hemorrhage. Another important finding of CT was old left temporal lobe infarction. Cerebral angiography detected right middle cerebral artery aneurysm at the trifurcation and moderate cerebral vasospasm of the right M2 portion. Neck clipping was successfully performed, but small size of right temporal lobe infarction was found on postoperative CT, which was due to cerebral vasospasm. Postoperative MRI showed bilateral temporal lobe infarction, especially including bilateral auditory cortex. This finding suggests that her deafness was cortical in origin.

Cerebral Infarction↗

Effective dose of granisetron for the prevention of post-operative nausea and vomiting in patients undergoing laparoscopic cholecystectomy.

This study was undertaken to determine the minimum effective dose of granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, for the prevention of post-operative nausea and vomiting (PONV) in female patients undergoing elective laparoscopic cholecystectomy. In randomized, placebo-controlled, double-blind study, 120 women were assigned to receive either placebo (saline) or granisetron at three different doses (20 micrograms kg-1, 40 micrograms kg-1 or 80 micrograms kg-1) intravenously immediately before the induction of anaesthesia. All patients received standardized anaesthesia consisting of isoflurane and nitrous oxide in oxygen. The incidence of PONV during the first 24 hours after anaesthesia was 43, 40, 13 and 13% after administration of placebo and granisetron 20 micrograms kg-1, 40 micrograms kg-1 and 80 micrograms kg-1, respectively (P < 0.05, overall Fisher's exact probability test). Adverse effects post-operatively were not different among the groups. In conclusion, granisetron 40 micrograms kg-1 is the minimum effective dose in the prevention of PONV after laparoscopic cholecystectomy.

Adult↗

[A case of Bartter's syndrome with chronic renal failure due to chronic interstitial nephritis].

We report a case of 45-year-old women with Bartter's syndrome and concomitant renal dysfunction. In 1986, the patient demonstrated muscle weakness and serum potassium levels as low as 1.1 mEq/l. She was suspected of having Bartter's syndrome because of hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normotension. Pretibial edema developed in 1989 for which she received 40 to 100 mg/week of furosemide intermittently for the next 5 years. Her serum potassium level ranged from 1.5 to 3.9 mEq/l. In 1991, her serum creatinine level rose to 2.1 mg/dl, then continued to increase gradually. She was admitted to our hospital in 1994 for evaluation of the renal dysfunction. Decreased creatinine clearance (44 ml/min) and a defect in urinary concentrating capacity (Fishberg's test, 370 mOsm/kg.H2O) were detected. Renal biopsy revealed juxtaglomerular cell hyperplasia. These findings resulted in the diagnosis of Bartter's syndrome. The renal biopsy also showed diffuse interstitial fibrosis and marked tubular atrophy. We postulate in this case that long-term hypokalemia due to Bartter's syndrome and the administration of furosemide led to chronic interstitial nephritis and renal dysfunction.

Bartter Syndrome↗

[High dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) For advanced testicular cancer].

Five patients with metastatic testicular cancer of advanced extent according to the Indiana University criteria were enrolled into this study. All tumors were non-pretreated non-seminomas. Initially all patients were treated with standard dose etoposide, ifosfamide and cisplatin (VIP) regimen. The response of two cycles of VIP was evaluated by tumor markers and diagnostic imagings. Two of the five patients showed a good response to VIP and subsequently achieved a pathological complete response (pCR) following surgical resection of residual masses after 3 or 5 courses of VIP. However, they suffered from severe myelosuppression and underwent peripheral blood stem cell transplantation (PBSCT) following the final course of VIP. The remaining three patients unlikely to be cured by VIP underwent chemotherapy consisting of high dose ICE:ifosfamide (6-10 g/m2 over 4days) carboplatin (1,500 mg/m2 over 4 days), etoposide (1,600-2,400 mg/m2 over 4 days) combined with PBSCT. This regimen resulted in one partial response (PR) with marker-negative and two PR with marker-positive. Residual masses were removed in all three patients and viable tumor cells were found in two. Of the five patients enrolled, four patients (80%) remain disease-free with minimal follow-up of 20 months, and the remaining one died of cancer 10 months after PBSCT. No serious side effects or complications were encountered. This study shows that standard dose induction therapy of VIP followed by early salvage chemotherapy of high dose ICE with PBSCT is well tolerated and effective in the treatment of advanced poor-risk testicular cancer.

Adult↗

[Treatment of non-thymic malignant tumors of the mediastinum].

Nonthymic malignant tumors of the mediastinum are quite rare. Primary mediastinal malignant lymphomas, malignant mediastinal neurogenic tumors, and primary malignant mediastinal mesenchymal tumors are reviewed and discussed in terms of the problems in their treatment.

Adolescent↗

[Hepatic resection for advanced carcinoma of the gallbladder].

Hepatic resection for advanced carcinoma of the gallbladder must be decided upon based on the modes of cancer spread to the liver. The cystic vein through the liver bed is considered an important route of liver metastasis, because liver metastases of gallbladder carcinoma are found frequently around the liver bed. About 70% of early metastatic foci demonstrated microscopically occur in segments 4a and 5. Resection of segments 4a and 5 is considered to be an adequate range of hepatectomy for patients with subserosal invasion, because early metastatic foci are detected not only in patients with direct invasion of the liver but also in those without direct invasion. For patients with direct liver invasion, various degrees of hepatic resection are needed to comply with the depth of direct invasion. It is necessary to achieve negative surgical margins 2 cm from the tumor. Because cancer cells extend along the Glissonian sheath in patients with hilar invasion, extended right hepatectomy with caudate lobectomy is required in these patients. A future problem is to establish the safety of extended hepatectomy in these patients.

Gallbladder Neoplasms↗

Antiviral effects of 6-chloro-2',3'-dideoxyguanosine in rhesus monkeys acutely infected with simian immunodeficiency virus.

A lipophilic dideoxynucleoside analogue, 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG), was expected to be effective against AIDS-related dementia. In this study, we tested the effect of 6-Cl-ddG on simian immunodeficiency virus (SIVmac239) replication in vitro and on acute infection of six rhesus monkeys (Macaca mulatta) with SIVmac239. This compound inhibited SIV-induced cytopathic effect in CEM x 174 cells and SIV replication in vitro with an ED50 value of 2.5 microM. A dose of 25 mg/kg 6-Cl-ddG was administered to three monkeys every 8 h for 10 days and an untreated group of three monkeys was injected with the solvent without drug. Although 6-Cl-ddG was not detected in the plasma, the metabolite ddG was maintained at a concentration of more than 3 microM for 8 h after administration. In the cerebrospinal fluid, the ddG concentration was 2 microM at 2 h after administration. SIV antigen (p27) and antibody appearance in the plasma were delayed for 5-8 days compared with the mock-treated group. The occurrence of lymphadenopathy in treated monkeys was delayed for 6 days compared with the mock-treated group. Signs of 6-Cl-ddG toxicity were minimal after the treatment. The results of this study provide further evidence that 6-Cl-ddG may act as a potent anti-human immunodeficiency virus agent in vivo.

Animals↗

Developmental changes in the electrical activity of locus coeruleus neurons during cortical spreading depression.

A previous study has demonstrated that during cortical spreading depression (CoSD), locus coeruleus (LC) neurons in adult rats reveal antidromic burst activity consisting of multiple initial segment (IS) spikes and IS-somatodendritic (SD) spikes with a distinct IS-SD break. In addition, the spontaneous firing rate of the neurons was reduced during CoSD. In the present experiments, we studied developmental changes in the electrical activity of LC neurons during CoSD. Since stable and repetitive DC shifts occurred in rats older than postnatal day 13 (PD13), the electrical activity of LC neurons at developmental stages later than PD13 was examined. The CoSD-related burst activity similar to that observed in adults was recorded at all stages of development, and the proportion of LC neurons showing the burst activity was nearly the same through all developmental stages and in adults. The frequency of IS spikes in the burst activity at PD13-P15 was not different from that in adults. However, the spontaneous firing rate of LC neurons at early developmental stages remained unchanged during CoSD. Based on these findings, it is conceivable that the mechanism of the generation of multiple IS spikes during CoSD at early developmental stages is different from that at later developmental stages and in adults.

Analysis of Variance↗

Prostaglandin E1 protects against ischemia-reperfusion injury of the liver by inhibition of neutrophil adherence to endothelial cells.

BACKGROUND: This study investigates the protective mechanism of prostaglandin E1 (PGE1) against hepatic ischemia-reperfusion injury in vivo. It has been demonstrated that activated leukocytes contribute to ischemia-reperfusion injury, and that administration of the monoclonal antibody (mAb) for adhesion molecules reduces the injury by inhibiting leukocyte-endothelial cell adhesion. We therefore attempted to find out whether PGE1 has an effect on the inhibition of neutrophil adherence to endothelial cells after reperfusion. METHODS: We administered anti-intercellular adhesion molecule 1 (ICAM-1) mAb, antiserum against rat polymorphonuclear leukocytes, or PGE1 to a rat model of left lobar ischemia for 60 min followed by reperfusion. Leukocyte adherence was observed by intravital fluorescence microscopy. The effect of PGE1 on the expression of adhesion molecules was analyzed by immunohistochemistry and flow cytometry. RESULTS: Ischemia-reperfusion caused endothelial dysfunction and hepatocellular injury with leukostasis in postsinusoidal venules. Anti-ICAM-1 mAb administration or leukopenia ameliorated both the hepatocellular injury and endothelial dysfunction. Although PGE1 administration did not affect the serum interleukin-8 level, it significantly decreased hepatic injury and leukostasis in the reperfused liver. Immunohistochemical findings showed that PGE1 decreased ICAM-1 expression on endothelial cells, but did not affect lymphocyte function-associated antigen 1, and membrane attack complex 1 on neutrophils in flow cytometric analysis. CONCLUSIONS: We conclude that PGE1 protects the liver against ischemia-reperfusion injury by reducing leukocyte-endothelial cell adhesion via down-modulation of ICAM-1 expression on the endothelium.

Alprostadil↗

Efficacy of 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG) on rhesus macaque monkeys chronically infected with simian immunodeficiency virus (SIVmac239).

To assess the therapeutic effects of 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG), a lipophilic dideoxynucleoside analogue, three rhesus macaques chronically infected with simian immunodeficiency virus (SIVmac239) were subcutaneously administered 25 mg/kg of the drug every 8 hours for 2 weeks. In two of three animals, the viral RNA in plasma and the cell-associated viral load from peripheral blood mononuclear cells were markedly decreased and the number of CD4+ and CD8+ lymphocytes were increased after 6-Cl-ddG administration. The decrease of the virus copies was associated with a reciprocal increase in the number of CD4+ lymphocytes. Additionally, a limiting dilution assay revealed a marked decrease in the lymph node cell-associated virus titer during the treatment. However, in the third monkey, the baseline of the number of CD4+ and CD8+ lymphocytes was higher than that of the other monkeys; these numbers changed very little during the treatment. In this monkey, the plasma SIV RNA level was decreased at the first week and was the same as the pretreatment level at the second week of the 6-Cl-ddG administration. In all three treated monkeys, the number of SIV RNA copies in the cerebrospinal fluid also tended to decrease during the 6-Cl-ddG treatment.

Animals↗

p16INK4, pRB, p53 and cyclin D1 expression and hypermethylation of CDKN2 gene in thymoma and thymic carcinoma.

There have been few reports on genetic alterations in thymomas. To investigate the expression of p16INK4A, RB, p53 and cyclin D1 in thymomas, we first examined 36 thymomas (non-invasive type, 16 cases; invasive type, 20 cases) and 3 thymic carcinomas, using immunohistochemistry. Abnormal expression of p16INK4A, RB, p53 and cyclin D1 was observed in 18, 8, 10 and 7 cases, respectively. Only a subgroup of invasive thymomas and thymic carcinomas showed an inverse correlation between p16INK4A and RB expression. Subsequently, we examined the 36 thymomas and 4 thymic carcinomas for mutations in p53 and CDKN2 genes, using PCR-SSCP and direct-sequencing analyses. No mutation of these genes was detected in the thymomas and thymic carcinomas examined. A polymorphism in the 3' untranslated region of exon 3 of CDKN2 was detected in 5 cases of thymoma. We searched for hypermethylation in the promoter region of CDKN2, observing it in 4 thymomas and 1 thymic carcinoma. Our data suggest that, unlike other more common cancers, alteration of the p53 gene may not play a significant role in the tumorigenesis of thymoma. However, inactivation of p16INK4A and RB may play a role in the progression of thymoma and thymic carcinoma.

Blotting, Southern↗

Cloning and crystal structure of hematopoietic prostaglandin D synthase.

Hematopoietic prostaglandin (PG) D synthase is the key enzyme for production of the D and J series of prostanoids in the immune system and mast cells. We isolated a cDNA for the rat enzyme, crystallized the recombinant enzyme, and determined the three-dimensional structure of the enzyme complexed with glutathione at 2.3 A resolution. The enzyme is the first member of the sigma class glutathione S-transferase (GST) from vertebrates and possesses a prominent cleft as the active site, which is never seen among other members of the GST family. The unique 3-D architecture of the cleft leads to the putative substrate binding mode and its catalytic mechanism, responsible for the specific isomerization from PGH2 to PGD2.

Animals↗

Phosphorylation of the Sendai virus M protein is not essential for virus replication either in vitro or in vivo.

A large proportion of intracellular Sendai virus (SeV) M proteins is phosphorylated, but in mature virions the M protein is not phosphorylated or dephosphorylated. Phosphorylated M protein in cells is bound to the cytoskeletal components more firmly than unphosphorylated M protein. Thus it has been hypothesized that M protein phosphorylation plays an important role in the virus life cycle, especially in the step of maturation. Here, a transient expression-mutation experiment of the M gene demonstrated that a change of the Ser residue at the 70th position from the N-terminus to Ala (S70A) totally abolished M protein phosphorylation, strongly suggesting that this residue is phosphorylated. The mutated M gene was then placed in the corresponding region in the cDNA plasmid which generates a full-length antigenome SeV RNA, and a mutant SeV M-S70A was successfully recovered from the cDNA. This mutant virus was indeed defective in M protein phosphorylation but did not differ at all from the wild-type SeV recovered from the parental cDNA either in the replication kinetics and plaque morphology in cultured cells or in in vivo replication and pathogenicity for mice. We thus concluded that no phosphorylation of the M protein was required for SeV replication either in vitro or in vivo.

Animals↗

Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules.

Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed on cancer cell membranes and activates the zymogen of MMP-2 (gelatinase A). We have recently isolated MT1-MMP complexed with tissue inhibitor of metalloproteinases 2 (TIMP-2) and demonstrated that MT1-MMP exhibits gelatinolytic activity by gelatin zymography (Imai, K., Ohuchi, E., Aoki, T., Nomura, H., Fujii, Y., Sato, H., Seiki, M., and Okada, Y. (1996) Cancer Res. 56, 2707-2710). In the present study, we have further purified to homogeneity a deletion mutant of MT1-MMP lacking the transmembrane domain (DeltaMT1) and native MT1-MMP secreted from a human breast carcinoma cell line (MDA-MB-231 cells) and examined their substrate specificities. Both proteinases are active, without any treatment for activation, and digest type I (guinea pig), II (bovine), and III (human) collagens into characteristic 3/4 and 1/4 fragments. The cleavage sites of type I collagen are the Gly775-Ile776 bond for alpha1(I) chains and the Gly775-Leu776 and Gly781-Ile782 bonds for alpha2(I) chains. DeltaMT1 hydrolyzes type I collagen 6.5- or 4-fold more preferentially than type II or III collagen, whereas MMP-1 (tissue collagenase) digests type III collagen more efficiently than the other two collagens. Quantitative analyses of the activity of DeltaMT1 and MMP-1 indicate that DeltaMT1 is 5-7.1-fold less efficient at cleaving type I collagen. On the other hand, gelatinolytic activity of DeltaMT1 is 8-fold higher than that of MMP-1. DeltaMT1 also digests cartilage proteoglycan, fibronectin, vitronectin and laminin-1 as well as alpha1-proteinase inhibitor and alpha2-macroglobulin. The activity of DeltaMT1 on type I collagen is synergistically increased with co-incubation with MMP-2. These results indicate that MT1-MMP is an extracellular matrix-degrading enzyme sharing the substrate specificity with interstitial collagenases, and suggest that MT1-MMP plays a dual role in pathophysiological digestion of extracellular matrix through direct cleavage of the substrates and activation of proMMP-2.

Collagen↗

Lineage- and differentiation stage-specific expression of LSM-1 (LPAP), a possible substrate for CD45, in human hematopoietic cells.

CD45, a transmembrane tyrosine phosphatase, is found on almost all nucleated hematopoietic cells and plays a crucial role in lymphocyte activation and differentiation. We recently achieved isolation of the human LSM-1 (hLSM-1) gene, whose product is a possible substrate for CD45, and we raised antibodies against the hLSM-1 protein. hLSM-1 expression in hematopoietic cells was examined with Northern and Western blot, fluorescence-activated cell sorter, and immunocytochemical analyses. It was found that in the lymphoid lineage, T and B lymphocytes as well as NK cells expressed LSM-1, whereas terminally differentiated plasma cells did not. As for the myeloid lineage, immature myeloid cells expressed LSM-1, whereas terminally differentiated granulocytes and monocytes did not. In the erythroid lineage, normal erythroblasts expressed very low levels of LSM-1, while erythroid cell lines (K562 and HEL) did not. Megakaryocytes did not express LSM-1. Both CD34+/CD33- and CD34+/CD33+ hematopoietic progenitor cells weakly expressed LSM-1. These results showed that LSM-1 is expressed in a lineage- and differentiation stage-specific fashion.

Blotting, Western↗