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Biomedical subjects

T Fujii

Publications and source records attributed to T Fujii.

At least 487 records · Page 27Linked to original sources
PubMed1997

Multidrug Resistance and Prodrug Activation for Cancer Gene Therapy of Breast Cancer.

Current approaches to the treatment of cancer (radiation and chemotherapy) are limited by the toxicity to normal tissues and the sensitivity of tumor cells to these treatments. The use of gene delivery vector systems for the introduction of genetic elements into normal and neoplastic tissues which code for proteins that protect the normal chemotherapy-sensitive tissues and sensitize the tumor cells to radiation and chemotherapy, may contribute to an overall improvement in the outcome of cancer treatment programs. This chapter will review the clinical trials either completed or about to be initiated which are designed to accomplish these goals.

Journal Article↗
PubMed1997

Sodium sensitivity and cardiovascular events in patients with essential hypertension.

BACKGROUND: In patients with sodium-sensitive hypertension, glomerular pressure is increased and microalbuminuria, a marker of glomerular hypertension, is a predictor of cardiovascular events. Similarly, the lack of a nocturnal decrease in blood pressure in these patients is also associated with an increased risk of cardiovascular events. We hypothesised that sodium sensitivity may be the common factor and carried out a retrospective study of cardiovascular events in patients with essential hypertension who had had sodium sensitivity measured in our clinic. METHODS: Sodium sensitivity was assessed in about 350 patients with essential hypertension during the initial investigation of their disorder. The definition of sodium sensitivity was a 10% or greater difference in blood pressure on low-sodium or high-sodium diets. By alphabetical order, the records of 201 patients were obtained and 156 patients without pre-existing disorders were followed up. The records of patients who had a cardiovascular event or died were reviewed without knowledge of the patient's sodium-sensitivity status. FINDINGS: 62 patients were deemed sodium sensitive and 94 non-sodium sensitive. Left-ventricular hypertrophy was found more frequently in the sodium-sensitive group than in the non-sodium-sensitive group (38 vs 16%; p < 0.01), whereas significantly fewer patients in this group smoked (23 vs 42%; p < 0.05). There were 17 cardiovascular events in the sodium-sensitive group and 14 in the non-sodium-sensitive group. The rate of total, non-fatal and fatal cardiovascular events, was 2.0 per 100 patient-years in the non-sodium-sensitive group and 4.3 per 100 patient-years in the sodium-sensitive group. Cox's proportional-hazards model identified sodium sensitivity (p < 0.01), mean arterial pressure (p < 0.01), and smoking (p < 0.01) as independent cardiovascular risk factors. INTERPRETATION: Cardiovascular events occurred more frequently in patients with sodium-sensitive hypertension. Sodium sensitivity is an independent cardiovascular risk factor in Japanese patients with essential hypertension.

Adult↗
PubMed1997

Polyadenylation-mediated translational regulation of maternal P450(11beta) mRNA in frog oocytes.

Northern blot analysis of bullfrog tissues using a cDNA probe of cytochrome P450(11beta) showed that a large amount of message was present in the ovary as well as in the adrenal tissue. Two kinds of mRNA of different sizes were found in the ovary. Sequence determination of the two cDNAs and analysis by reverse-transcription polymerase chain reaction indicated that the protein encoded by the larger mRNA was identical to the adrenal enzyme, while the protein encoded by the smaller had a truncated sequence lacking an extension peptide necessary for the protein transport to the mitochondria. The mRNAs were present in the oocytes but not in the follicular cells, and their content in an oocyte varied little during its maturation. Immunoblot analyses of the mitochondrial fraction of oocytes failed to demonstrate the presence of P450(11beta) protein. In contrast the eggs were found to contain a large amount of enzymatically active protein. Interestingly the mRNA has a cis-element called cytoplasmic polyadenylation element at its 3' untranslated region. When poly(A) tails of the message prepared from eggs and oocytes were examined by RNase H digestion or reverse-transcription polymerase chain reaction, those of eggs were about 150 nucleotides longer than those of oocytes. These results suggest that translation of the message is stimulated during the oocyte maturation as a result of enhanced polyadenylation at its 3'-end. Finally a finding is presented that progesterone was converted to 11beta-hydroxyprogesterone by the frog P450(11beta), implying that the enzyme expressed in eggs may control a level of progesterone which is needed to initiate the oocyte maturation.

Animals↗
PubMed1997

Auditory evoked magnetic fields in patients with right hemisphere language dominance.

Auditory evoked magnetic fields for pure-tone stimuli were measured in seven subjects with right hemisphere dominance for language using a whole-head magnetoencephalography system linked to magnetic resonance imaging. N100m responses were observed in both hemispheres in five subjects. The N100m response latency to contralateral stimulation was significantly shorter on the right than on the left in all cases. Normal right-handed subjects with left hemisphere dominance showed exactly the same responses. Therefore, the shorter N100m latency in the right hemisphere is independent of the dominant hemisphere for language.

Acoustic Stimulation↗
PubMed1997

Sodium restriction shifts circadian rhythm of blood pressure from nondipper to dipper in essential hypertension.

BACKGROUND: Sodium restriction has been widely used for treatment of hypertension and renal diseases. Whether sodium restriction can transform the circadian rhythm of blood pressure from nondipper to dipper is examined. METHODS AND RESULTS: Patients (n=42) with essential hypertension were maintained on a high-sodium diet (12 to 15 g of NaCl per day) and a low-sodium diet (1 to 3 g/d) for 1 week each. On the last day of each diet, blood pressures were measured noninvasively every hour for 24 hours with an automatic oscillometric device. Twenty-one patients were classified as non-sodium sensitive whereas 21 were classified as sodium sensitive on the basis of a > or = 10% change in 24-hour mean arterial pressure caused by sodium restriction. Nocturnal blood pressure fall was significant in the non-sodium sensitive subjects but not in sodium-sensitive subjects. There was a significant interaction between sodium restriction and nocturnal fall in blood pressure only in the sodium-sensitive subjects, indicating that the degree of the nocturnal fall was affected by sodium restriction. Furthermore, changes in the nocturnal fall induced by sodium restriction had a positive relationship with sodium sensitivity (r=.38, P<.02) and a negative relationship with the nocturnal fall before sodium restriction (r=-.75, P<.0001). CONCLUSIONS: These findings show the difference in nocturnal fall in blood pressure between the non-sodium sensitive and sodium-sensitive types of essential hypertension. The diminished nocturnal fall, recognized in the sodium-sensitive type, is restored by sodium restriction, indicating that the circadian rhythm of blood pressure shifted from a nondipper to a dipper pattern. On the other hand, the nocturnal fall is not affected by sodium restriction in the non-sodium sensitive type, and the circadian rhythm remains of the dipper variety.

Adult↗
PubMed1997

Presence of NF-kappaB-like and IkappaB-like immunoreactivities in postsynaptic densities.

The distributions of IkappaB and NF-kappa B immunoreactivities were examined immunohistochemically in the rat brain by the electron microscopy. Antibodies were raised against synthetic peptides with the sequences specific to the human MAD-3 type IkappaB or NF-kappa B. Both IkappaB alpha and NF-kappa B immunoreactivities were localized in the dendrites including the spines and, particularly, the postsynaptic densities (PSDs) of the hippocampus and the cerebral cortex. The PSD fraction prepared from the rat brain contained an activity that inhibited the binding of NF-kappa B to the kappa B DNA elements. These results suggest that the NF-kappa B/IkappaB system or a similar mechanism may play a role in signal transmission from synapses to the nucleus.

Amino Acid Sequence↗
PubMed1997

Excitable membranes and synaptic transmission: postsynaptic mechanisms. Localization of alpha-internexin in the postsynaptic density of the rat brain.

The synaptic localization of alpha-internexin, a brain-specific intermediate filament protein, was investigated immunohistochemically in the rat brain. The specificity of the antibody used in this study was confirmed by Western blotting and the antibody specifically reacted with alpha-internexin in the neurofilament preparation and in the postsynaptic density (PSD) fraction. The alpha-internexin immunoreactivity was distributed in neurons, especially in the somata and dendrites, throughout the cerebral cortex. Immunoelectron microscopic examination showed the immunoreactivity in the PSD, while neurofilament M was not in the PSD. Thus alpha-internexin and neurofilament M are differentially localized in neuronal cells. Alpha-internexin content in the PSD fraction was relatively high even before the period of synaptogenesis and the content in the fraction was unchanged between young and adult rats (2-6 weeks old). These results suggest a role of alpha-internexin for early development and organization of the PSD.

Amino Acid Sequence↗
PubMed1997

Demonstration of the facilitatory role of 8-OH-DPAT on cholinergic transmission in the rat hippocampus using in vivo microdialysis.

The role of the serotonin (5-HT)1A receptor in the regulation of acetylcholine (ACh) release in the hippocampus was investigated using an in vivo microdialysis technique and a sensitive radioimmunoassay specific for ACh. The mean (+/- S.E.M.) basal ACh contents in the hippocampal perfusate of conscious, freely moving rats was 60 +/- 4 (n = 29) and 3691 +/- 265 fmol/30 min (n = 31), respectively, in the absence and presence of physostigmine (Phy) in the perfusion fluid. Systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.5 mg/kg, s.c.), a 5-HT1A agonist, significantly enhanced ACh release both in the presence and absence of Phy. Local application of 8-OH-DPAT (3-30 microM) into the hippocampus through the microdialysis probe significantly potentiated ACh release only in the presence of Phy, whereas no significant effect was observed in its absence. Pretreatment with NAN-190 (3 mg/kg, i.p.), a 5-HT1A antagonist, eliminated the increasing effect of systemically applied 8-OH-DPAT on ACh release, while NAN-190 alone had no effect on basal ACh release either in the absence or presence of Phy. Consistent with the time course of ACh release, systemic administration of 8-OH-DPAT evoked hyperlocomotion, which was reversed by NAN-190. However, local hippocampal application of 8-OH-DPAT did not affect the locomotor activity of the rats. These findings suggest that at least two different sites are involved in the 8-OH-DPAT-induced increase in the release of ACh in the rat hippocampus in vivo.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Nitric oxide increases stimulation-evoked acetylcholine release from rat hippocampal slices by a cyclic GMP-independent mechanism.

Nitric oxide (NO) is an endothelium-derived relaxing factor and its main mechanism of action is activation of soluble guanylyl cyclase. NO and NO-related compounds have been reported to affect several neuronal functions in the central nervous system. In this study, we investigated the effects of NO donors (sodium nitroprusside (SNP) and (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409)) on acetylcholine (ACh) release from rat hippocampal slices. SNP (10(-5) M) and FK409 (10(-4) M) increased electrical stimulation-evoked ACh release without affecting basal release. As dibutyryl cyclic GMP inhibited stimulation-evoked ACh release, the effects of these NO donors were not due to soluble guanylyl cyclase activation. Atropine increased stimulation-evoked ACh release by blocking presynaptic muscarinic autoreceptors, and SNP increased stimulation-evoked ACh release in the presence of atropine, suggesting that SNP and atropine increase stimulation-evoked ACh release by different mechanisms. The present results indicate that NO enhances some part of the excitation-secretion coupling pathway without inducing ACh release directly and these effects are mediated by cyclic GMP-independent mechanism.

Acetylcholine↗
PubMed1997

Maintenance of constant blood acetylcholine content before and after feeding in young chimpanzees.

We have shown that acetylcholine (ACh) is present in the blood of various species of mammals using a specific, sensitive radioimmunoassay. In the present study, the effect on blood and plasma ACh levels of feeding after overnight fasting was studied in one male and five female 4- to 7-year-old chimpanzees. The mean basal ACh concentrations of the blood and plasma were 3143 +/- 380 and 184 +/- 10 pg/ml (+/-SEM, n = 6), respectively. Feeding each chimpanzee 500 g boiled sweet potatoes as breakfast at 1000 h and tap water given ad libitum did not affect the ACh content of the blood and plasma, and constant values of the blood and plasma ACh contents were observed for 4 h after the feeding. Hematocrit and plasma acetylcholinesterase (AChE) activity were also insensitive to feeding. No correlation was observed between plasma AChE activity and either blood or plasma ACh content. The results of the present study indicate that the blood ACh of chimpanzees is distributed mainly in the blood cell fraction, and that the blood ACh content is not regulated directly by cholinergic nerve activity or by plasma AChE activity.

Acetylcholine↗
PubMed1997

Oral administration of KW-5092, a novel gastroprokinetic agent with acetylcholinesterase inhibitory and acetylcholine release enhancing activities, causes a dose-dependent increase in the blood acetylcholine content of beagle dogs.

Acetylcholine (ACh) was detected in the blood and plasma of beagle dogs using a specific, sensitive radioimmunoassay. The mean basal ACh contents in the blood and plasma of beagle dogs were 451 +/- 65 and 83.5 +/- 12.3 pg/ml (+/- SEM, n = 7), respectively, and were lower than the contents in humans reported previously by our laboratory. Oral administration of KW-5092 (10-30 mg/kg), a gastroprokinetic agent with acetylcholinesterase (AChE) inhibitory and ACh release enhancing activities, caused a dose-dependent increase in the ACh content of both the blood and plasma, as well as several behavioral side effects due to peripheral cholinergic stimulation. The size of the increase in the plasma ACh content at each dose of KW-5092 was greater than that in the blood, indicating that KW-5092 caused the increase in the blood ACh content through elevation of the plasma ACh content, by inhibition of AChE and facilitation of ACh release. These results demonstrate that the blood ACh of beagle dogs is present mainly in the blood cells and to a lesser degree in the plasma, and that KW-5092 increased the blood ACh content mainly by increasing the plasma ACh concentration.

Acetylcholine↗
PubMed1997

Effects of aminoguanidine on systemic inflammatory response syndrome induced by platelet activating factor and by lipopolysaccharide in rats.

We investigated the effects of aminoguanidine, a relatively selective inhibitor of inducible nitric oxide (NO) synthase, on the systemic inflammatory response syndrome induced by platelet activating factor (PAF) and by lipopolysaccharide in rats, with emphasis on NO production in vivo. Aminoguanidine treatment improved survival rates after lipopolysaccharide challenge, whereas it aggravated the lethality caused by PAF. Lipopolysaccharide induced a marked increase in the concentrations of nitrate and nitrite in plasma compared with vehicle administration, and the increase was prevented by aminoguanidine. In contrast, PAF challenge with or without aminoguanidine did not affect the concentrations of nitrate and nitrite in plasma compared with vehicle administration. These results suggest that NO derived from inducible NO synthase is not a major participant in the systemic inflammatory response syndrome induced by PAF. Aminoguanidine is not likely to provide beneficial effects in conditions where PAF is produced and the concentrations of nitrate and nitrite in plasma are not significantly increased.

Animals↗
PubMed1997

Different roles of the left and right parahippocampal regions in verbal recognition: a PET study.

We examined the role of the parahippocampal regions in humans during two types of verbal recognition process, i.e. delayed matching and non-matching, by measuring regional cerebral blood flow (rCBF) using PET. The results showed differential activation of each parahippocampal region during verbal memory tasks in which the side activated shifted depending on the nature of the task employed; an increase in rCBF in the left parahippocampal gyrus was associated with retrieval strategy of non-matching, and an increase in rCBF in the right parahippocampal gyrus was associated with retrieval strategy of matching. We conclude that lateralized parahippocampal activation may depend on the type of response required.

Adolescent↗
PubMed1997

The crystal structure of zinc-containing ferredoxin from the thermoacidophilic archaeon Sulfolobus sp. strain 7.

The crystal structure of ferredoxin from the thermoacidophilic archaeon Sulfolobus sp. strain 7 was determined by multiple isomorphous replacement supplemented with anomalous scattering effects of iron atoms in the Fe-S clusters, and refined at 2.0 A resolution to a crystallographic R value of 0.173. The structural model contains a polypeptide chain of 103 amino acid residues, 2 [3Fe-4S] clusters, and 31 water molecules; in this model, the cluster corresponding to cluster II in bacterial dicluster ferredoxins loses the fourth iron atom although it may originally be a [4Fe-4S] cluster. The structure of the archaeal ferredoxin consists of two parts: the core fold part (residues 37-103) and the N-terminal extension part (residues 1-36). The "core fold" part has an overall main-chain folding common to bacterial dicluster ferredoxins, containing two clusters as the active center, two alpha-helices near the clusters, and two sheets of two-stranded antiparallel beta-sheet (the terminal and central beta-sheets). The "N-terminal extension" part is mainly formed by a one-turn alpha-helix and a three-stranded antiparallel beta-sheet. The beta-sheet in the N-terminal extension is hydrogen-bonded with the terminal beta-sheet in the core fold to form a larger beta-sheet. The distinct structural feature of this archaeal ferredoxin lies in the zinc-binding center where the zinc ion is tetrahedrally ligated by four amino acid residues (His 16, His 19, and His 34 from the N-terminal extension, and Asp 76 from the core fold). The zinc ion in the zinc-binding center is located at the interface between the core fold and the N-terminal extension, and connects the beta-sheet in the N-terminal extension and the central beta-sheet in the core fold through the zinc ligation. Thus, the zinc ion plays an important role in stabilizing the structure of the present archaeal ferredoxin by connecting the N-terminal extension and the core fold, which may be common to thermoacidophilic archaeal ferredoxins.

Amino Acid Sequence↗
PubMed1997

Fluorescent diagnosis of experimental gastric cancer using a tumor-localizing photosensitizer.

To clarify the usefulness of fluorescent diagnosis for gastric cancer, we assessed the sensitivity and specificity of the tumor-localizing photochlorine photosensitizer ATX-S10 in combination with a new fluorescence diagnostic system. Into the submucosa of the stomachs of five rabbits, VX-2 tumor cells originating from squamous cell carcinoma were injected. After 3 weeks, three rabbits (Group I) were sacrificed 3 h after intravenous injection of ATX-S10 at a dose of 20 mg/kg, and their stomachs were observed by the Hg-lamp-induced fluorescence diagnostic system. The other two rabbits (Group II) were also sacrificed without injection of ATX-S10 and observed by the same method. In all cases in Groups I and II, gastric cancers that were invaded from the submucosa to the serosa were recognized histologically. The concentration of ATX-S10 examined by high-performance liquid chromatography (HPLC) in the gastric cancer was significantly higher than in the normal stomach. Fluorescent spectroscopy could detect 630 nm fluorescence selectively, consistent with the cancerous tissue of Group I. Moreover, fluorescent images were detected in only the exposed area of cancerous tissue and were undetected in the surrounding normal mucosa. Conversely, no fluorescent images could be detected in the stomachs of Group II. It is suggested that a fluorescence diagnostic system using ATX-S10 may become useful for the diagnosis of the existence or extension of carcinoma of the gastrointestinal tract.

Animals↗
PubMed1997

Splenic hamartoma associated with thrombocytopenia.

A case of splenic hamartoma associated with thrombocytopenia is reported. A 70-year-old man was referred to our hospital because of carcinoma of the body of the pancreas. Hematological examination disclosed thrombocytopenia and elevated serum CA19-9 and Span-1 levels. In addition to typical findings of pancreatic carcinoma, a solid mass was observed in the spleen by imaging procedures. On ultrasonography, the splenic mass was well demarcated and slightly hypoechoic. Computed tomography demonstrated a homogeneous low-density mass 5 cm in diameter. On T1- and T2-weighted magnetic resonance images, the splenic mass was demonstrated as low intensity and high intensity, respectively. On selective angiography, the tumor was hypervascular. Distal pancreatectomy plus splenectomy was performed. Microscopically, the splenic tumor consisted of red pulp tissue and was diagnosed as splenic hamartoma.

Aged↗
PubMed1997

Alpha-fetoprotein-producing carcinoma of the colon: report of a case.

We report herein the rare case of a 67-year-old man in whom alpha-feto-protein (AFP)-producing carcinoma originated in the transverse colon, describing the clinical course of the patient and the histological features of the tumor. At the age of 63, the patient had been diagnosed as having sigmoid colon carcinoma, and surgery was carried out. However, 4 years later, his fecal occult blood test was positive, and further investigation revealed a transverse colon carcinoma with liver metastasis. The serum AFP measured preoperatively was 10978 ng/ml. Resection of the transverse colon and a liver biopsy were performed, following which his serum AFP level decreased to 4804 ng/ml. Histology of the ulcerated lesion in the transverse colon showed a poorly differentiated adenocarcinoma with a medullary growth pattern. Using an immunohistochemical staining method, AFP-producing cells were detected in the transverse colon carcinoma and the liver metastasis. Based on our experience of this patient and a review of the literature on the few cases previously reported, we conclude that AFP-producing coloretal carcinoma has a tendency to produce blood-borne metastasis and to be associated with a poor prognosis.

Aged↗