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Biomedical subjects

M Fujii

Publications and source records attributed to M Fujii.

At least 415 records · Page 23Linked to original sources

Flow cytometric analysis of nuclear DNA content in tissues of colon cancer using endoscopic biopsy specimens.

Flow cytometric assay of nuclear DNA in endoscopic biopsy specimens was evaluated in colon cancer patients. When the cells were divided into diploid cells and aneuploid cells, aneuploidy was observed in 63% (58 of 92) of the colon cancer patients. However, no clear relation was observed between the frequency of aneuploidy and the invasive depth, size, or histological type of colon cancer. Noncancerous portions of the colon tissues including colon adenoma or normal mucosa were mostly (96%, 87 of 91) diploid. Nuclear DNA content could be analyzed in the fresh biopsy specimens of colon cancer tissues and such investigation might be possibly valuable for further biological characterization of colon cancer in the usual procedure of clinical diagnosis for colonic malignancy before surgical operation or other treatment.

Adenoma↗

Chronic oral administration of synthetic trypsin inhibitor camostate reduces amylase release from isolated rat pancreatic acini.

In the present study, we examined stimulus-secretion coupling in pancreatic acini prepared from rats given synthetic protease inhibitor camostate at a dose of 200 mg/kg body wt by an orogastric tube once a day for 10 d. Camostate treatment significantly increased pancreatic weight, protein, DNA, and enzyme contents. In acini prepared from the camostate-treated rats, responsiveness to both CCK-8 and carbamylcholine was greatly decreased with no shift in the dose-response curves compared to control acini prepared from saline-treated rats. There were no major changes in the affinity for both high- and low-affinity sites of CCK receptors, but there was a significant reduction in the capacity of low-affinity site based on acinar protein. Responsiveness to secretin in the camostate-treated rat acini was also significantly reduced compared with that in the controls. However, amylase release from the camostate-treated rat acini in response to an increase in intracellular calcium levels induced by the calcium ionophores A23187 or to an increase in intracellular cyclic 3',5'-monophosphate (cyclic AMP) levels caused by 8 bromo cyclic AMP was not significantly different from the control rat acini, suggesting that both Ca(2+)-dependent tyrosine kinase and nucleotide-activated kinases are not impaired. On the other hand, the responsiveness to phorbol ester TPA, which stimulates amylase secretion via a calcium-independent cascade by activating protein kinase C directly, was reduced in the camostate-treated rat acini compared with the controls. These results suggest the possibilities that the reduced amylase secretion in the camostate-treated rats is owing to alterations in both the transmembrane signal transduction and the phosphorylation of regulatory proteins by the Ca(2+)-independent, protein kinase C-dependent mechanisms.

8-Bromo Cyclic Adenosine Monophosphate↗

Axons from the olfactory bulb transplanted into the hippocampal formation show axon preferences and form transplant-to-host synapses similar to those of normal afferents.

Using a mouse Thy-1 allelic system (an AKR strain of Thy-1.1 was used as the host and a BALB/c strain of Thy-1.2 as the graft), characteristics of transplant-to-host axon projection and synapse formation of the olfactory bulb (OB) were studied in the hippocampal formation by immunohistochemical and ultrastructural examinations. Thy-1.2-positive axon projections were most prominent in the dentate molecular layer (DM), although there was a labeled-axon-poor layer in the innermost part of the DM. Some of the axons in the DM entered the hippocampus proper, forming two clear borders between the two axon-rich outer layers and the inner axon-poor central layer. These results suggested that axons from the transplanted OB extended into the hippocampal formation, showing axon preferences. In the ultramicroscopic observation of the DM, three different synaptic patterns could be distinguished among the transplant-to-host synapses. These three synaptic patterns are similar to those of the synapses formed by perforant path fiber terminals in the DM, indicating that the transplanted OB forms fiber connections with the dendrites of the dentate granule neurons similar to those of normal afferents.

Animals↗

Molecular cloning of cDNA encoding a bovine selenoprotein P-like protein containing 12 selenocysteines and a (His-Pro) rich domain insertion, and its regional expression.

When cDNA containing proteins enriched in the bovine cerebellar cortex were cloned, a clone which seemed to encode a selenoprotein P-like protein was isolated. The coding nucleotide sequence of its cDNA insert displayed high homology to rat and human selenoprotein P cDNA but contained 12 rather than 10 TGAs (12 rather than 10 selenocysteines in deduced amino acids), a tandem repeat of one CACTCC (His-Ser) and seven CATCCCs (His-Pro), and a 3' untranslated region approximately 890 bases shorter than that of rat liver selenoprotein P. RT-PCR using a set of primers flanking to the repeat displayed the existence of mRNA without the repeat. The tandem repeat and its adjacent region consisted of a similar motif of CAC/TCC/AC/T. Thus, these proteins included a (His-Pro) rich domain with a slightly negative free energy change irrespective of having the tandem repeat or not. Such His-Pro repeats reportedly exist in the segmentation gene paired or homeobox protein Om(1D) of Drosophila. Moreover, both this selenoprotein P-like protein mRNA and selenoprotein P mRNA were expressed in all the areas of the brain but most prominently in the cerebellar cortex, hippocampus, and olfactory bulb. These findings suggest the possibility that these selenoproteins are major selenium carriers in the brain and play a role in the morphological response of nerve or glial cells.

Amino Acid Sequence↗

The electrophysiological effects of multiple subpial transection (MST) in an experimental model of epilepsy induced by cortical stimulation.

Multiple subpial transection (MST) is an effective surgical therapy for patients with intractable seizures whose epileptogenic lesions lie in the cortex and are unresectable. Morrell developed this procedure and reported clinical results obtained using it. However, only the disappearance of epileptiform discharges after MST in an experimental model of epilepsy has been demonstrated. The aim of this study was to establish the histological changes caused by MST and evaluate the effects of this procedure on interneuronal discharge spread in an epilepsy model, i.e. acute cortical kindling in rabbits. Histologically, vertical cracks in the transected cortex with mild gliosis and very little tissue disruption were observed. Horizontal fibers across the crack had been transected, whereas vertical fibers and neuronal cell bodies were preserved. The stimulation-induced after-discharges (ADs) were analyzed: cortical hyperactivity across the transected zone was reduced significantly earlier than that in the control group. Propagation of ADs induced by the kindling effect was also inhibited. These results suggest that MST interrupts not only neuronal synchronization, but also excitatory interneuronal conduction, in this epilepsy model.

Animals↗

CYP52 (cytochrome P450alk) multigene family in Candida maltosa: identification and characterization of eight members.

Previously, we characterized three genes and presented evidence for an n-alkane-inducible cytochrome P450 (P450alk) multigene family in an n-alkane-assimilating and diploid-type yeast, Candida maltosa. In the present report, we isolated and characterized additional members of this gene family, including a total of thirteen P450alk-related sequences (eight genes and five of their alleles). Two sets, each consisting of two genes, were tandemly arranged in the genome. A gene replacement experiment showed that at least one gene had only a single allele in the genome. The determined nucleotide and the deduced amino acid sequences indicated that all had a characteristic constituent for P450s and exhibited amino acid identities from 94% to 37% to each other. Six genes showed relatively higher similarities to each other than to the other two genes and were thus classified into a subfamily. All the members of this subfamily were assigned to the same single chromosome, showing a good correlation between sequence similarity and chromosomal linkage. Although all the genes except for one were induced by n-alkane, their inducibilities by some other aliphatic carbon sources showed variabilities.

Alleles↗

A high degree of sequence homology in the putative carbohydrate recognition domains of pokeweed mitogen and wheat germ agglutinin: poly-N-acetyllactosamine-binding lectins from different species.

The complete amino acid sequence of a poly-N-acetyllactosamine-binding pokeweed mitogen 4 (Pa-4) was determined using a protein sequencer. After digestion of Pa-4 with endoproteinase Lys-C, Asp-N, Arg-C or Glu-C, the resulting peptides were separated by reversed-phase high-performance liquid chromatography (HPLC) and then subjected to sequence analysis using a protein sequencer. The complete amino acid sequence of Pa-4 was found to exhibit a high degree of homology with that of wheat germ agglutinin (WGA) regarding their overall sequences and the spatial arrangement of cysteine-glycine. Furthermore, the amino acid residues of WGA directly involved in carbohydrate-binding sites were found in the homologous region in Pa-4. This is the first report to show that lectins from different plant families (Phytolaccaceae for Pa-4 and Gramineae for WGA) possess homologous primary sequences.

Amino Acid Sequence↗

Genetic complementation of the immortal phenotype in group D cell lines by introduction of chromosome 7.

Human immortal cell lines have been classified into at least four (A-D) genetic complementation groups by cell-cell hybrid analysis, i.e., a hybrid derived from different groups becomes mortal. Recently we have demonstrated that introduction of human chromosome 7 suppresses indefinite division potential in the non-tumorigenic human immortalized fibroblast lines KMST-6 and SUSM-1, both assigned to complementation group D. By extending our microcell-mediated chromosome transfer, we found that chromosome 7 also suppresses division potential in the human hepatoma line HepG2 (again, assigned to group D). Chromosome 7 was thus shown to suppress indefinite growth in the above group D cell lines irrespective of their cell types, or whether they are tumorigenic or not. Since chromosome 7 had no such effect on representative cell lines derived from complementation group A, B or C, these results indicate that the senescence gene(s) commonly mutated in the group D cell lines is located on chromosome 7.

Base Sequence↗

Non-X histiocytoma, similar to fibrous histiocytoma, in an infant.

A case is presented of a female infant with an atypical histiocytoma. A gradually enlarging brown lesion was noted on the left side of the chest at the age of 2 weeks. Microscopic study of a biopsy revealed an ill-defined infiltration of spindle cells with indented nuclei. The tumor cells were positive for CD14, HLA-DR, lysozyme, alpha-1-antitrypsin and alpha-1-antichymotrypsin, and negative for CD1, CD3, CD8, CD10, CD19, CD68 and S-100 by immunohistochemistry. Electron microscopy demonstrated no distinct Birbeck's granules, but aberrant granules were seen in a small number of cells. At 7 months of age, a nodule with similar histologic features was noted in the nuchal region, but was incompletely resected. The patient remains recurrence-free at 36 months of age. This case is thought to be a benign form of non-X histiocytoma.

Diagnosis, Differential↗

Retinopathy and subconjunctival haemorrhage in patients with chronic viral hepatitis receiving interferon alfa.

A total of 43 patients (86 eyes) with chronic viral hepatitis were examined prospectively before and after the start of interferon therapy. Of 37 non-diabetic patients, 23 (group A1) did not have retinopathy or subconjunctival haemorrhage, 11 (group A2) developed retinopathy, and three (group A3) exhibited subconjunctival haemorrhage during the treatment. In most eyes, the retinopathy disappeared after therapy was stopped. Of six diabetic patients, three (group B1) developed retinopathy and three (group B2) showed progression of existing retinopathy. Thrombocytopenia was not associated with the retinopathy in any patient. The patients' good visual acuity remained unchanged, even after retinal changes appeared. Ophthalmologists should be aware that retinopathy and subconjunctival haemorrhage may develop in patients with chronic viral hepatitis receiving interferon therapy.

Adult↗

Evaluation of pancreatic tumors with positron emission tomography and F-18 fluorodeoxyglucose: comparison with CT and US.

PURPOSE: To assess the clinical value of positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose (FDG) for identification of pancreatic carcinoma. MATERIALS AND METHODS: Forty-six patients suspected of having a pancreatic neoplasm and who were to undergo surgery prospectively underwent FDG PET, computed tomography (CT), and transabdominal ultrasound (US). Endoscopic US was performed in 40 patients. Images were independently interpreted and compared with the histopathologic findings at surgery (41 patients) or with clinical follow-up findings (five patients). RESULTS: In 33 of 35 patients, foci of pancreatic carcinomas (10-100 mm in diameter) were identified as an increase in FDG uptake, whereas CT, transabdominal US, and endoscopic US depicted the foci in 31, 31, and 28, cases, respectively. Among 11 benign lesions, nine showed no increased FDG uptake (specificity = 82%). Specificities of the other modalities were lower. False-positive findings were obtained in a case of chronic active pancreatitis and in a serous cystadenoma. CONCLUSION: FDG PET, which provides "biochemical" information, is accurate in identifying pancreatic carcinoma and may be a method of choice when imaging equivocal masses detected with other "anatomic" imaging studies.

Adenocarcinoma↗

c-Jun, c-Fos and their family members activate the transcription mediated by three 21-bp repetitive sequences in the HTLV-I long terminal repeat.

Transcription of human T-cell leukemia virus type I is regulated by a viral transactivatior Tax, through the 21-bp sequence in the long terminal repeat (LTR). We found that cellular transcription factor AP-1 (c-Jun/c-Fos heterocomplex) bound to the 21-bp sequence. The binding affinity of the complex increased in proportion to the number of the 21-bp sequence, and the transcriptional activation by AP-1 became evident only when the reporters had more than three 21-bp sequences. Thus, AP-1 may play a role in the viral transcription from the LTR with three 21-bp sequences in the absence of Tax, such as in the early stage of the virus infection.

Amino Acid Sequence↗

Japanese pharmacy: innovation mixed with tradition.

OBJECTIVE: To report the current status of pharmacy practice in Japan. DATA SOURCES: Published conference reports, journal articles, human resource consultation with medical and pharmacy practitioners, and site visitation by the authors. DATA EXTRACTION AND SYNTHESIS: Data on areas related to Japanese history, practice of pharmacy, and professional innovations were obtained through interviews and the literature. Information is provided to give an appreciation of current pharmacy practice in Japan. CONCLUSIONS: Japanese pharmacy practice is a strong combination of tradition and professional innovation. The potential for professional growth is immense; Japanese pharmacy has successfully established payment for nondistributive pharmacy services. Payment for cognitive services creates many positive incentives for the future practice of pharmacy in Japan.

Computers↗

Synthesis and structure-activity studies of a series of 1-oxa-8-azaspiro[4.5]decanes as M1 muscarinic agonists.

2,8-Dimethyl-1-oxa-8-azaspiro[4,5]decan-3-one (17), designed by incorporating the tetrahydrofuran ring moiety of muscarone into an 8-azaspiro[4,5]decane skeleton, and related 1-oxa-8-azaspiro[4.5]decanes were synthesized and assessed as M1 muscarinic agonists for the symptomatic treatment of dementia of Alzheimer's type. The compounds were tested for central muscarinic M1 and M2 receptor affinity and in vivo muscarinic activities: namely, amelioration of scopolamine-induced impairment in rat passive avoidance tasks, and induction of hypothermia, tremor, and salivary secretion. Compound 17 exhibited potent muscarinic activities in vitro and in vivo with no selectivity. Systematic modifications of 17 were conducted, and a number of compounds, including the 2-ethyl analogue (18), 3-methylene analogue (29), 3-dithioketal analogues (26, 28), and 3-oxime analogue (37) were found to display preferential affinity for M1 receptors over M2 receptors and, in addition, to exhibit potent antiamnesic activity sufficiently separated from hypothermia-inducing activity, taken as an index of cholinergic side effects, compared with the reference compound RS86 (1). Structure-activity relationships are discussed in comparison with those for muscarone analogues. Of these compounds only two, 2-ethyl-8-methyl-1-oxa-8-azaspiro[4.5]decan-3-one (18) and 2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane (29), stimulated phosphoinositide hydrolysis in rat hippocampal slices, indicating partial agonistic activity for M1 muscarinic receptors. The optical resolution of 18 and 29 was performed. Eudismic ratios of both compounds in binding affinity were low, but M1 agonist activity resided preferentially in the (-)-isomers. The absolute configuration of (-)-29 was determined by X-ray crystal structure analysis to be S, being the same as that of muscarone. Based on the in vivo selectivity, (-)-29 was selected for clinical studies.

Alkanes↗

Role of skeletal muscle metabolism in exercise capacity of patients with myocardial infarction studied by phosphorus-31 nuclear magnetic resonance.

Patients with congestive heart failure reportedly show a poor correlation between cardiac function and exercise tolerance. Recent studies have demonstrated that skeletal muscle is the main factor that limits exercise tolerance. However, the relationship between high-energy phosphate metabolism in skeletal muscle and exercise tolerance has not been well defined. Exercise capacity was assessed in 35 subjects with myocardial infarction in terms of peak oxygen consumption (peak VO2) during treadmill exercise with an analysis of expired gases. On the same day, changes in high-energy phosphates in finger flexor muscle during handgrip exercise were measured by magnetic resonance spectrometry. Phosphocreatine (PCr) utilization and the decrease in pH during handgrip exercise were significantly greater in patients with a poor exercise capacity and their time constant of recovery of PCr was prolonged. The ratios of PCr/Pi (Pi: inorganic phosphate) and PCr/HMPA (HMPA: hexamethylphosphoramide) during exercise and the time constant of recovery of PCr were significantly correlated with peak VO2. These results suggest that skeletal muscle metabolism governs exercise tolerance.

Adult↗

Rectus hematoma secondary to vomiting: a complication of conditioning regimen for bone marrow transplantation.

A 41-year-old woman with chronic myelogenic leukemia was scheduled to undergo transplantation of bone marrow. The patient complained of nausea and vomiting following the initiation of chemotherapy. One day prior to the planned termination of chemotherapy, the patient developed left-sided abdominal pain. Physical examination and imaging examination indicated the possibility of acute abdomen associated with bleeding or herniation. For therapeutic and diagnostic purposes, an emergency operation was performed. A 6 x 5 cm hematoma was detected within the left rectus abdominis muscle. It is suggested that the gastrointestinal symptoms should be carefully controlled in patients undergoing bone marrow transplantation.

Adult↗

Postcholecystectomy syndrome mimicking angina pectoris detected by the morphine provocation test.

A 66-year old woman had had intermittent anterior chest pain and upper abdominal pain for 15 years. Angina pectoris was diagnosed at the age of 51 years, as she had typical anginal pain that was relieved by nitroglycerine, although coronary arteriography was normal and the ergonovine provocative test was negative. She had undergone cholecystectomy at the age of 38 years. Her bile duct pressure increased markedly after morphine injection and severe pain with the aforementioned distribution was produced. Postcholecystectomy syndrome due to sphincter of Oddi spasm was diagnosed and her pain was relieved by endoscopic sphincterotomy.

Aged↗

Apneic spells in a patient with myelomeningocele without Chiari type II malformation--case report.

A female neonate with myelomeningocele but without Chiari type II malformation suffered from apneic spells. Magnetic resonance imaging showed no obvious brainstem anomaly. Brainstem auditory evoked potentials were initially abnormal and subsequently deteriorated during the 6 months after birth. The brainstem deficits were not reversed by a ventriculoperitoneal shunt. She died of respiratory distress and cardiac failure at 2 years of age. This case indicates an intrinsic dysfunction in the brainstem of patients with myelomeningocele not complicated by Chiari type II malformation.

Arnold-Chiari Malformation↗