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Biomedical subjects

T Fujii

Publications and source records attributed to T Fujii.

At least 163 records · Page 9Linked to original sources
PubMed2001

Isolated and focal retrograde amnesia: a hiatus in the past.

Two cases of isolated retrograde amnesia were reported. Both showed the same clinical pattern in development and resolution of amnesia despite of different etiologies. Sudden insult to the brain (trauma in Case 1 and viral encephalitis in Case 2) caused concurrent antero- and retrograde amnesia. Fortunately both recovered from the anterograde amnesia completely. However, both were left with a period of postictal amnesia of a few months and retrograde amnesia of up to 14 months' duration. The analysis of their pattern of temporal evolution and dissolution of amnesia support the hypothesis that recently acquired episodic information requires a certain amount of constant activation for a certain period of time in order to be organized into a durable memory. The nature of this activation as well as its origin remains to be solved.

Accidents, Traffic↗
PubMed2001

Comparison of TaqMan Salmonella amplification/detection kit with standard culture procedure for detection of Salmonella in meat samples.

We evaluated the TaqMan PCR Salmonella amplification/detection kit (PE Applied Biosystems) for rapid detection of Salmonella from a variety of meat samples. This system uses the 5' nuclease activity of Taq DNA polymerase, which digests an internal fluorogenic probe to monitor the amplification of the target gene. The detection sensitivity of the kit, using 2 kinds of DNA extraction protocols, was compared with that obtained with 4 protocols of official culture methods. A total of 98 meat samples (16 raw beef, 31 pork and 51 chicken) were tested. The results of the TaqMan PCR method and the combined results of the 4 cultural protocols showed excellent agreement. However, no single culture protocol showed optimal recovery of Salmonella comparable to the PCR method. These results suggest that the TaqMan PCR method is a reliable and rapid method useful for detecting Salmonella in meat products.

Food Microbiology↗
PubMed2001

Underexpression of cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in serous ovarian carcinomas.

Reduced expression of a cyclin-dependent kinase inhibitor, p27, has been reported to be associated with poor prognosis in several human cancers. The aim of this study was to investigate the potential role of p27 in ovarian cancer development and progression. Immunohistochemical expression of p27 was determined using 117 epithelial ovarian tumor tissues and 8 normal ovaries. p27 mRNA expression was examined by semi-quantitative PCR amplification using 26 ovarian cancer samples. Nuclear staining of p27 was commonly observed in the normal ovarian surface epithelium and the epithelial cells of germinal inclusion cysts. Positive p27 staining rates were significantly higher in serous adenomas (p=0.006) and in serous LMP tumors (p=0.013) than that in serous carcinomas (Fisher's exact test). In serous ovarian cancers, positive p27 staining rate was significantly higher in early stage (stage1/2) than that in advanced stage (stage 3/4) diseases (p=0.030, Fisher's exact test). Log-rank testing showed that negative p27 expression significantly correlates with poor survival in serous ovarian cancer patients (p=0.041). Considerable levels of p27 mRNA were detected in all ovarian cancer samples examined. These results suggest that the underexpression of p27 caused by post-translational mechanism may contribute to the development and progression and result in poor prognosis of serous ovarian cancers.

Cell Cycle Proteins↗
PubMed2001

Expression of G1 cell cycle markers and the effect of adenovirus-mediated overexpression of p21Waf-1 in squamous cell carcinoma of the esophagus.

To determine the crucial abnormality in the cell cycle regulatory proteins in human squamous cell carcinoma of the esophagus, we examined the cell growth ratio (CGR) and basal expression levels of G1 cyclins (cyclin D1, cyclin E), cyclin-dependent kinase (cdk) 2, cdk4, proliferating cell nuclear antigen (PCNA), and p21Waf-1 using 9 cell lines (KE3, KE4, TE8, TE9, TE10, TE11, YES1, YES2, and YES6). Western blotting revealed an inverse linear correlation between the basal levels of p21Waf-1 expression and CGR. The protein levels of G1 cyclins, cdks, and PCNA did not coordinately reflect the CGR. There was no relationship between p21Waf-1 expression levels and mutation of the p53 gene. Next, when the cells were stimulated with serum 48 h after the starvation, stimulated levels of the above G1 cell cycle markers were variously observed among cell lines irrespective of CGR. Serum stimulation markedly induced phosphorylated Rb in TE9 (a high CGR cell line, CGR>2.0), but not in KE4 (a low CGR cell line, CGR<1.5). Furthermore, adenovirus-mediated expression of exogenous p21Waf-1 effectively reduced cell growth in KE3 and TE9 (high CGR cell lines), but not in KE4 and TE11 (low CGR cell lines). p21Waf-1-mediated growth suppression was associated with the induction of involucrin, a marker of squamous cell differentiation. Our data suggested that the basal level, but not the stimulated level, of p21Waf-1 expression play a pivotal role in abnormal growth in human squamous cell carcinoma of the esophagus.

Adenoviridae↗
PubMed2001

[A breast cancer patient with recurrence in the thoracic wall in whom a high-dose of toremifene was effective].

The patient was a 53-year-old female who presented with a primary complaint of reddening of the left precordial skin. She had undergone mastectomy for cancer of the left breast 12 years and 4 months earlier and had received endocrine chemotherapy including TAM as a postoperative adjuvant therapy. A diagnosis of thoracic wall recurrence was made by chest CT and pathological examination of skin biopsy specimens. Toremifene (TOR) was administrated at 120 mg/day, and PR was maintained for 8 months. Even after the condition became PD, the patient has retained adequate QOL with combination therapies including radiotherapy, and is still treated on an outpatient basis 3 years after the beginning of the treatment.

Antineoplastic Agents, Hormonal↗
PubMed2001

[A case of crossed aphasia with echolalia after the resection of tumor in the right medial frontal lobe].

We report a right-handed woman, who developed a non-fluent aphasia after resection of astrocytoma (grade III) in the right medial frontal lobe. On admission to the rehabilitation department, neurological examination revealed mild left hemiparesis, hyperreflexia on the left side and grasp reflex on the left hand. Neuropsychologically she showed general inattention, non-fluent aphasia, acalculia, constructional disability, and mild buccofacial apraxia. No other apraxia, unilateral spatial neglect or extinction phenomena were observed. An MRI demonstrated resected areas in the right superior frontal gyrus, subcortical region in the right middle frontal gyrus, anterior part of the cingulate gyrus, a part of supplementary motor area. Surrounding area in the right frontal lobe showed diffuse signal change. She demonstrated non-fluent aprosodic speech with word finding difficulty. No phonemic paraphasia, or anarthria was observed. Auditory comprehension was fair with some difficulty in comprehending complex commands. Naming was good, but verbal fluency tests for a category or phonemic cuing was severely impaired. She could repeat words but not sentences. Reading comprehension was disturbed by semantic paralexia and writing words was poor for both Kana (syllabogram) and Kanji(logogram) characters. A significant feature of her speech was mitigated echolalia. In both free conversation and examination setting, she often repeated phrases spoken to her which she used to start her speech. In addition, she repeated words spoken to others which were totally irrelevant to her conversation. She was aware of her echoing, which always embarrassed her. She described her echolalic tendency as a great nuisance. However, once echoing being forbidden, she could not initiate her speech and made incorrect responses after long delay. Thus, her compulsive echolalia helped to start her speech. Only four patients with crossed aphasia demonstrated echolalia in the literature. They showed severe aphasia with markedly decreased speech and severe comprehension deficit. A patient with a similar lesion in the right medial frontal lobe had aspontaneity in general and language function per se could not be examined properly. Echolalia related to the medial frontal lesion in the language dominant hemisphere was described as a compulsive speech response, because some other 'echoing' phenomena or compulsive behavior were also observed in these patients. On the other hand, some patients with a large lesion in the right hemisphere tended to respond to stimuli directed to other patients, so called 'response-to-next-patient-stimulation'. This behavior was explained by disinhibited shift of attention or perseveration of the set. Both compulsive speech responses and 'response-to-next-patient-stimulation' like phenomena may have contributed to the echolalia phenomena of the present case.

Adult↗
PubMed2001

[The usefulness of intra-operative angiography during off-pump CABG].

BACKGROUND: Recently OPCAB has become more and more common in CABG, although one problem of OPCAB like the quality of anastomosis has not been solved yet. We discussed the usefulness of intra-operative angiography during OPCAB. METHODS: During March 1997-July 2000, 55 patients underwent OPCAB (including 35 MIDCAB cases) in our institute. Graft flow and anastomosis were examined by intra-operative or immediate post-operative angiography. RESULTS: Immediate postoperative angiography was performed in 22 MIDCAB cases. In 15 cases an excellent graft flow without stenosis could be confirmed, in 7 cases the native LAD was so small, which caused a poor flow of the LITA and three cases needed additional PTCA because of anastomosis stenosis. Intra-operative angiography was done in 9 MIDCAB and 17 OPCAB. As a result, re-anastomosis was performed in one case of MIDCAB because of severe anastomosis stenosis, one case of OPCAB had confirmed poor flow because of a small LAD, but in 24 cases an excellent graft flow could be seen on time. In 2 cases OPCAB was combined with PTCA to achieve complete revascularization. CONCLUSIONS: Intra-operative angiography is a useful strategy to confirm the surgical results quickly in OPCAB (included MIDCAB). Using such a strategy, combination of OPCAB and PTCA as a new approach for complete revascularization can be performed safe and smooth.

Aged↗
PubMed2001

A novel cytochrome P450 enzyme responsible for the metabolism of ebastine in monkey small intestine.

Small intestinal microsomes of cynomolgus monkeys were found to catalyze hydroxylation and dealkylation of an H(1)-antihistamine prodrug, ebastine. To identify the main enzyme responsible for ebastine hydroxylation, which has been hitherto unknown, we purified two cytochrome P450 isoforms, named P450 MI-2 and P450 MI-3, from the intestinal microsomes on the basis of the hydroxylation activity. P450 MI-2 and P450 MI-3 showed the respective apparent molecular weights of 56,000 and 53,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The internal amino acid sequence of P450 MI-2 had high similarity with those of human CYP4F2, CYP4F3, and CYP4F8. The first 27 amino acid residues of P450 MI-3 were highly homologous with those of monkey CYP3A8 and human CYP3A4/5/7. Furthermore, P450 MI-2 and P450 MI-3 were recognized by anti-CYP4F and anti-CYP3A antibodies, respectively, in immunoblot analysis and catalyzed leukotriene B(4) omega-hydroxylation and testosterone 6beta-hydroxylation, which are known to be mediated by CYP4F and CYP3A, respectively. Although both enzymes had ebastine hydroxylation activity, the V(max) value of P450 MI-2 was much higher than that of P450 MI-3 (37.0 versus 0.406 nmol/min/nmol of P450), and the former K(M) (5.1 microM) was smaller than the latter K(M) (10 microM). Anti-CYP4F antibody inhibited the hydroxylation in small intestinal microsomes strongly (70%), but anti-CYP3A antibody did not. These results indicate that P450 MI-2 belongs to the CYP4F subfamily and is mainly responsible for hydroxylation of ebastine in monkey small intestinal microsomes. This suggests that the small intestinal CYP4F enzyme, P450 MI-2, can play an important role in the metabolism of drugs given orally.

Amino Acid Sequence↗
PubMed2001

[Clinical efficacy of treatment with low-dose flutamide in maximum androgen blockade therapy].

To prevent treatment withdrawal due to flutamide-induced liver dysfunction, we performed maximum androgen blockade (MAB) therapy by combining a luteinizing hormone-releasing hormone agonist or orchiectomy with low-dose flutamide (125 mg x 2/day) in patients with prostate cancer. In this study, the efficacy, adverse effects such as hepatotoxicity, and compliance were compared retrospectively between 35 patients who received low-dose flutamide therapy (1995-1999) and 27 patients who received flutamide at its ordinary dose (125 mg x 3/day). No significant difference was observed in the response rate (> or = PR) as determined from the prostate-specific antigen parameter (p = 0.6211) or the incidence of hepatotoxicity based on the aspartate aminotransferase and alanine aminotransferase levels. However, flutamide withdrawal due to liver dysfunction was less frequent in the low-dose group (2.9%) than in the ordinary dose group (18.5%) (p = 0.0386). MAB therapy using low-dose flutamide is expected to prevent the reduction in the compliance due to side effects and to improve the long-term prognosis in patients with prostate cancer, who are mostly elderly individuals.

Aged↗
PubMed2001

Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.

We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.

Adolescent↗
PubMed2001

[Experimental gene therapy using p21/WAF1 gene in esophageal squamous cell carcinoma--adenovirus infection and gene gun technology].

p21/WAF1 (p21) inhibits the activity of the cyclin/cdk complex and controls the G1 to S cell phase transition. In the present study, we used a recombinant adenoviral approach and gene gun technology to introduce p21 into esophageal cancer cells in order to assess the effect of p21 on cell growth. Infection with the p21 adenovirus (AdV) using gene gun technology resulted in inhibition of TE9 and KE3 cell growth. The levels of involucrin, which is a marker of squamous epithelium differentiation, markedly increased at 48 h and 72 h after p21 AdV infection in TE9 cells. These results indicate that p21 plays an important role in esophageal cancer cell proliferation. Overexpression of the p21 gene can inhibit cell growth and induce differentiation in esophageal cancer cells. p21 gene therapy may prove beneficial in the treatment of esophageal cancer.

Adenoviridae↗
PubMed2001

[Seizure and developmental prognosis of West syndrome--combination therapy with high-dose vitamin B6, valproate and low-dose ACTH].

Twenty patients with West syndrome were initially treated with high-dose vitamin B6 (40 to 50 mg/kg/day) and valproate (40 to 50 mg/kg/day). Three became seizure free. For the remaining 17 patients, low-dose synthetic ACTH (0.01 mg [0.4 IU]/kg/day) was added to the regimen. One month after the end of ACTH therapy, 13 patients were seizure free. Thus 16 patients in total(80%) were free of seizures(group A). The treatment was ineffective for the remaining 4 patients (20%; group B). During the following for a mean period of 64 months (range, 48 to 83 months), 9 in group A had a relapse of epileptic seizures. However, only 4 in this group had epileptic seizures at the end of the study (5-7 years of age), all of which were partial and infrequent. In group B, two had frequent intractable seizures, and one was seizure free at the end of the study. One died at the age of 1 year. In group A, 2 patients showed normal or subnormal mental development. Mild, moderate and severe mental retardation were seen in 3, 4 and 7 patients respectively. In group B, all patients showed severe mental retardation. In this study, the rate of evolution into intractable epilepsy was low, but long-term mental development was poor. Seizure control by itself seemed to be insufficient to improve long developmental prognosis of West syndrome.

Adrenocorticotropic Hormone↗
PubMed2001

[Breast cancer].

Neoadjuvant chemotherapy (NAC) represents a new approach based on sound theoretical, pharmacokinetic, and experimental principles. The purpose of NAC is to improve control of the primary site by downstaging and to improve control of micrometastatic disease. NAC has been standard therapy in the management of locally advanced breast cancer. Patients with earlier stage breast cancer may also benefit from treatment with NAC. Recently some investigators have mentioned that NAC can be used instead of adjuvant chemotherapy and would be most appropriate for patients who wish to preserve their breast but who have tumors too large for breast conserving surgery. In this article, we reviewed the present status of NAC (indication, clinical response, pathologic response, survival, possibility of breast conservation, prognostic/predictive factors, neoadjuvant endocrine therapy) and discussed several unanswered questions on NAC (survival benefit, optimal number of treatment cycles, optimal regimens) and future direction. Combined modality therapy including NAC appears to provide excellent local control, the possibility of breast conservation, and, probably, an increased survival rate, at least for some subsets of patients. Furthermore, through sequential sampling, NAC provides indeed the opportunity to identify molecular mechanisms associated with pathologic response and to study the possibility to guide the choice for induction treatment and patient populations submitted to neoadjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Qualitative features of confabulation in a case with basal forebrain amnesia].

We investigated qualitative features of confabulation in a case with basal forebrain amnesia. A 66-year-old, right-handed woman with a 8th-grade education, was admitted to the Rehabilitation Department of Tohoku University Hospital, Japan, for evaluation and therapy of amnesia. Her previous medical history included hypertension. Nine months before admission, she went to a hospital because of headache and blurred vision. She was diagnosed as suffering from a suprasellar arachnoid cyst and unruptured aneurysm at the anterior communicating artery. Five months later, resection of the cyst and clipping of the aneurysm was performed. After the operation, she became disoriented and amnesic with marked confabulation. On admission to our hospital 3 months later, she was alert and cooperative. Detailed neuropsychological assessment was performed during the next two months. She remained clinically stable throughout her hospitalization. Neurological examination showed no abnormalities. Brain magnetic resonance images revealed lesions in the bilateral orbito-frontal cortices and basal forebrain. Measurement of blood flow with 123I-IMP single photon emission computed tomography showed hypoperfusion in the bilateral frontotemporal regions. We performed systematic investigations to clarify the qualitative features of her confabulations. Her confabulations included many facts she had experienced before, but they were out of context. Each fact was recalled in isolation or associated with erroneous places, persons or times. Her confabulations were never fantastic or momentary in nature, but were consisted with isolated facts. Experimental investigation revealed that she could recognize individual facts (a person, a place, a task and time) in each episode. However, she could not integrate individual facts into an episode. We propose calling this type of confabulation "mosaic confabulation".

Aged↗
PubMed2000

Crystal structures of the transposon Tn5-carried bleomycin resistance determinant uncomplexed and complexed with bleomycin.

The transposon Tn5 carries a gene designated ble that confers resistance to bleomycin (Bm). In this study, we determined the x-ray crystal structures of the ble gene product, designated BLMT, uncomplexed and complexed with Bm at 1.7 and 2.5 A resolution, respectively. The structure of BLMT is a dimer with two Bm-binding pockets composed of two large concavities and two long grooves. This crystal structure of BLMT complexed with Bm gives a precise mode for binding of the antibiotic to BLMT. The conformational change of BLMT generated by binding to Bm occurs at a beta-turn composed of the residues from Gln(97) to Thr(102). Crystallographic analysis of Bm bound to BLMT shows that two thiazolium rings of the bithiazole moiety are in the trans conformation. The axial ligand, which binds a metal ion, seems to be the primary amine in the beta-aminoalanine moiety. This report, which is the first with regard to the x-ray crystal structure of Bm, shows that the bithiazole moiety of Bm is far from the metal-binding domain. That is, Bm complexed with BLMT takes a more extended form than the drug complexed with DNA.

Acetyltransferases↗
PubMed2000

Pharmacology of the receptors for the phorbol ester tumor promoters: multiple receptors with different biochemical properties.

The phorbol ester tumor promoters and related analogs are widely used as potent activators of protein kinase C (PKC). The phorbol esters mimic the action of the lipid second messenger diacylglycerol (DAG). The aim of this commentary is to highlight a series of important and controversial concepts in the pharmacology and regulation of phorbol ester receptors. First, phorbol ester analogs have marked differences in their biological properties. This may be related to a differential regulation of PKC isozymes by distinct analogs. Moreover, it seems that marked differences exist in the ligand recognition properties of the C1 domains, the phorbol ester/DAG binding sites in PKC isozymes. Second, an emerging theme that we discuss here is that phorbol esters also target receptors unrelated to PKC isozymes, a concept that has been largely ignored. These novel receptors lacking kinase activity include chimaerins (a family of Rac-GTPase-activating proteins), RasGRP (a Ras exchange factor), and Unc-13/Munc-13 (a family of proteins involved in exocytosis). Unlike the classical and novel PKCs, these "non-kinase" phorbol ester receptors possess a single copy of the C1 domain. Interestingly, each receptor class has unique pharmacological properties and biochemical regulation. Lastly, it is well established that phorbol esters and related analogs can translocate each receptor to different intracellular compartments. The differential pharmacological properties of the phorbol ester receptors can be exploited to generate specific agonists and antagonists that will be helpful tools to dissect their cellular function.

Animals↗
PubMed2000

Leukemia inhibitory factor gene improves skin allograft survival in the mouse model.

BACKGROUND: Leukemia inhibitory factor (LIF) is a widely expressed cytokine involved in both local and systemic immune response. Furthermore, it has been implicated in various immunological processes including thymic T cell maturation and embryo implantation. We investigated implication of various modalities in the application of prolonged and viable allograft to the wound, using cytokines and growth factors. MATERIALS: BALB/c and B6D2F1 strains of mice were used either as a skin graft donor or host. LIF cDNA inserted in plasmid vector or the vector alone was injected intradermally in graft skin and observed up to 21 days. LIF, LIF-receptor, gp130, as well as type 1 and 2 T helper cytokine expressions were investigated by reverse transcription polymerasse chain reaction, in situ hybridization, and histological studies. RESULTS: LIF cDNA-treated groups showed significantly improved graft survival compared to the vector-treated control in 21 days postoperatively for grafting from B6D2F1 to BALB/c and BALB/c to B6D2F1. LIF and LIF receptor mRNA expressions were observed 24 hr and 21 days posttransplantation. The gp130 expression was only observed in LIF-treated B6D2F1 to BALB/c allografting on day 21 posttransplantation. LIF transcripts were strongly present in the epidermal, dermal, and subdermal tissues as determined by an in situ hybridization of LIF-treated grafting. CONCLUSIONS: These results suggest that LIF cDNA treatment is an effective and beneficial adjuvant for the skin allograft survival. Improved skin allograft modulation by cytokine gene transfer is a potentially promising therapy for temporary large skin coverage.

Animals↗