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Biomedical subjects

Y Fujita

Publications and source records attributed to Y Fujita.

At least 73 records · Page 4Linked to original sources

A study of the combination of gemcitabine hydrochloride (LY188011) and cisplatin in non-small-cell lung cancer: 3-week schedule.

BACKGROUND: It has been reported that the combination of gemcitabine (LY188011; GEM) and cisplatin (CDDP) in a 4-week schedule showed a high response rate for patients with non-small-cell lung cancer (NSCLC), but GEM could not be administered on day 15 because of increased myelosuppression in many patients. The present study was performed to evaluate the efficacy and safety of GEM and CDDP in a 3-week schedule. METHODS: Patients with unresectable NSCLC without prior chemotherapy were enrolled. We administered 1000 mg/m2 of GEM on days 1 and 8, and 80 mg/m2 of CDDP on day 1. The feasibility of the combination therapy was confirmed in 8 patients, and then 20 more patients were enrolled, to evaluate the efficacy and safety of this combination therapy for all 28 patients. RESULTS: The response rate was 42.9% (12/28) and the median survival time was 12.6 months. Neutropenia, leukopenia, anemia, thrombocytopenia or lymphocytopenia of grade 3 or higher were observed as hematological toxicity, and anorexia, nausea, fatigue, or vomiting of grade 3 were the nonhematological toxicities, but most of these toxicities were of grade 2 or less. For GEM and CDDP, 89% and 91% of the scheduled doses, respectively, were administered. CONCLUSION: This is the first study of the combination of GEM and CDDP with a 3-week schedule in Japan, and the results showed a low level of myelosuppression, high dose intensity, and high response rate, similar to the results reported in other countries. Accordingly, the combination of GEM and CDDP with a 3-week schedule may be a promising regimen for the treatment of NSCLC in Japan.

Adult↗

Doppler velocimetry in the adrenal artery in human fetuses.

BACKGROUND: Fetal hypoxia and/or acidosis causes redistribution of blood flow to the high-priority organs including the adrenal glands. Although this phenomenon is well described in the human cerebral and placental circulations using Doppler velocimetry, there are few reports about the adrenal glands. AIM: To clarify the gestational age-related changes in adrenal blood flow in normal fetuses and fetuses at risk of hemodynamic derangement. MATERIAL AND METHODS: In 153 normal cases, the resistance indices (RIs) calculated from the blood flow velocity waveforms (FVWs) in the middle adrenal artery (MAA) were obtained from 24 weeks to construct nomogram using regression analysis. Twenty-seven complicated cases were divided according to the 5%ile RI values in the MAA, and clinical outcomes were retrospectively compared. RESULT: The RI values in the MAA increased until 31 weeks and decreased thereafter. The 50%ile regression curve was represented as RI=-0.000914 (weeks)(2)+0.0579 weeks-0.181. Of the 27 complicated cases, 13 had RIs in the MAA below the 5%ile. Cases with low RI had significantly higher RI ratio in regard of UA/MCA; higher occurrence of abnormal FHR patterns on observation; higher incidence of cesarean delivery for nonreassuring fetal well-being status; earlier gestational age at delivery; lower birth weights and longer periods of admission to NICU than the cases with normal RI. CONCLUSION: We have described the nomogram for the RI in the MAA. In conditions of fetal hypoxia or acidemia, blood flow redistribution to the adrenal glands may occur and the analysis of the adrenal artery FVWs may be useful in detection of fetal altered hemodynamics.

Adrenal Glands↗

Two mouse piwi-related genes: miwi and mili.

Genes belonging to the piwi family are required for stem cell self-renewal in diverse organisms. We cloned mouse homologues of piwi by RT-PCR using degenerative primers. The deduced amino acid sequences of mouse homologues MIWI and MILI showed that each contains a well-conserved C-terminal PIWI domain and that each shares significant homology with PIWI and their human counterparts HIWI. Both miwi and mili were found in germ cells of adult testis by in situ hybridization, suggesting that these genes may function in spermatogenesis. Furthermore, mili was expressed in primordial germ cells (PGCs) of developing mouse embryos and may therefore play a role during germ cell formation. MIWI may be involved in RNA processing or translational regulation, since MIWI was found to possess RNA binding activity. Our data suggest that miwi and mili regulate spermatogenesis and primordial germ cell production.

Amino Acid Sequence↗

Preparation and properties of thermosensitive hydrogel microcapsules.

Temperature-sensitive hydrophilic gel microcapsules have been newly prepared. That is, poly (L-lysineisopropylamide-terephthalic acid) microcapsules containing water have been obtained by an interfacial polymerization at a water/oil interface between L-lysineisopropylamide and terephthaloyldichloride. The microcapsule changes its size between 33 and 35 degrees C. Under 33 degrees C, the microcapsules are fully spherical and can be redispersed in distilled water, while are aggregated above 35 degrees C. The microcapsules, which are observed to show aggregation above 33 degrees C, can be redispersed by decreasing temperature within a few second. The thermosensitive morphological changes of the microcapsules are thus reversible. Also, it has been shown that the permeability of sodium chloride through the microcapsule membrane changes remarkably between 33 and 35 degrees C, while it is kept almost constant independent of temperature between 25 and 33 degrees C or between 35 and 55 degrees C. The permeability of solutes is higher under 33 degrees C than that above 35 degrees C. Such thermosensitive properties result from the fact that the polymer membrane has isopropylamide groups. That is, L-lysineisopropylamide has a chemical structure similar to N-isopropylacrylamide, the polymer of which, poly (N-isopropylacrylamide), is a thermosensitive hydrogel having its phase transition temperature around 33 degrees C.

Journal Article↗

An anaphylactic reaction possibly associated with an intraoperative coronary artery spasm during general anesthesia.

We report a case of anaphylactic reaction occurring during general anesthesia that may have been accompanied by a coronary artery spasm. The present case and a review of the medical literature suggest that coronary artery spasm is evoked by common vasoactive mediators with anaphylactic reactions. Coronary artery spasm should be counted as a symptom of the cardiovascular manifestation of anaphylaxis. Clinicians should be aware of this possible complication when treating an anaphylactic reaction, especially in patients at risk for atherosclerosis. Early recognition of ST segment elevation is essential for diagnosis and treatment of coronary artery spasm.

Aged↗

Reversible conformational change in beta-lactoglobulin A modified with N-ethylmaleimide and resistance to molecular aggregation on heating.

beta-Lactoglobulin A (beta LG A) modified with N-ethylmaleimide (NEM-beta LG A) was purified by ion exchange chromatography, and modification of beta LG A by NEM was confirmed by time of flight mass spectrometry and 5,5'-dithiobis(2-nitrobenzoic acid) methods. The fluorescent spectrum of NEM-beta LG A was slightly different from that of native beta LG A. NEM-beta LG A gave no polymerization after heating at 80 degrees C and pH 7.5, as shown by polyacrylamide gel electrophoresis. Conformational change of NEM-beta LG A was observed at 80 degrees C by ultraviolet differential spectra, whereas after cooling it recovered to its original state as before heating, indicating apparent reversible thermal denaturation. Native beta LG A is resistant to pepsin hydrolysis, whereas heated beta LG A was easily hydrolyzed by pepsin. NEM-beta LG A before heating was also resistant to pepsin hydrolysis, and after heating NEM-beta LG A was still resistant to pepsin hydrolysis. These results indicate that NEM-beta LG A maintained a conformation similar to its native form even after heating. Addition of 0.2 M NaCl to the beta LG A heated under salt-free condition induced polymerization of heated beta LG A molecules, but not that of heated NEM-beta LG A. This seemed to indicate that the formation of inter- or intramolecular disulfide linkage made the heat-induced conformational change of beta LG A irreversible.

Chromatography, Ion Exchange↗

Linkage of sugar chains to a fragment peptide of FGF-5S by a chemoenzymatic strategy and changes in the rate of proteolytic hydrolysis.

Various O-linked and N-linked sugar chains were linked enzymatically to a fragment peptide (Leu-Ser-Gln(or Asn)-Val-His-Arg) of FGF-5S. First, galactose was linked with beta-(1-->3)-linkage to GalNAc-linked peptide by a transglycosylation using beta-galactosidase from Bacillus circulans (recombinant). Then sialic acid was linked with the aid of sialyltransferase from rat liver (recombinant) to give NeuAcalpha-(2-->3)-Galbeta-(1-->3)-GalNAc-linked hexapeptide. Further, a sialylated 2-chain biantennary sugar chain was linked by a transglycosylation using endo N-acetyl-beta-D-glucosaminidase from Mucor hiemalis (endo M, recombinant). The activity of DNA synthesis in a fibroblast cell line was increased by this glycosylation. The resistance of the obtained glycopeptides towards proteolytic hydrolysis by rat serum and by five proteases was compared with that of original peptide. The resistance was remarkably enhanced by the glycosylation.

Animals↗

The dentofacial manifestations of XXXXY syndrome: a case report.

This paper presents a six-year-old patient with XXXXY syndrome, whose oral findings included a cleft soft palate, hyper- or meso-taurodontism in eight primary molars and in the mandibular permanent first molars, five congenitally missing premolars, and delayed development of the permanent tooth germs. The maxillary and mandibular primary central incisors were in a cross-bite relationship. Cephalometric findings showed a short ramus of the mandible and a short maxilla in the anterioposterior plane. The anteroposterior jaw relationship was in harmony. The cross-bite was considered to be due to the retroinclination of the maxillary primary incisors. This case emphasises the importance of regular dental care, and monitoring of facial growth and dental development in children with XXXXY syndrome.

Anodontia↗

Autocrine expression of neurotrophins and their receptors in prostate cancer.

Previously, it has been demonstrated that the neurotrophins and their receptors are present in human prostate tissue, but neither their functional role nor localization is clearly understood. We studied the expression of neurotrophins and their receptors in prostate cancer. Between 1990 and 1999, 48 prostate cancer specimens were obtained from patients undergoing radical prostatectomy, of whom 25 received neoadjuvant hormonal therapy (NHT) and 23 were untreated. The specimens were analyzed immunohistochemically for neurotrophins (nerve growth factor, brain derived neurotrophic factor, neurotrophin 3, neurotrophin 4/5) and their receptors (TrkA, TrkB, TrkC, p75NTR). Immunohistochemical studies revealed that both benign and malignant prostate gland epithelial cells expressed the neurotrophins and their receptors to various degrees, but no obvious immunopositive reaction was observed in stromal cells. In benign epithelial cells, the neurotrophins were localized to secretory cells and the receptors were localized to basal cells. The neurotrophins, TrkA and TrkC were expressed to a similar extent in prostate cancer specimens obtained from patients both with and without NHT. In contrast, the expression of TrkB was down-regulated and the expression of p75NTR was up-regulated in prostate cancer after hormonal therapy. These findings suggest that neurotrophins are secreted by prostate cancer cells in an autocrine fashion. Neurotrophins may be involved, through their receptors, in the escape mechanism from cell death after androgen depletion found in prostate cancer.

Aged↗

Evaluation of water and electrolyte transport of tubular epithelial cells under osmotic and hydraulic pressure for development of bioartificial tubules.

Our aim was to develop bioartificial tubules using tubular epithelial cells and artificial membranes and evaluate the function of water and electrolyte transport by various tubular epithelial cells. The cells were cultivated onto extracellular matrix (ProNectin F) coating polycarbonate membrane. Water transport from the apical to the basolateral site of cells was examined using a modified Ussing chamber module. Water transport under colloidal osmotic pressure on the apical site and hydraulic pressure on the basolateral site were higher in JTC-12, LLC-PK1 cells than in MDCK cells. Water transport under osmotic plus hydraulic pressure was highest in LLC-PK1 cells. We made bioartificial tubules using LLC-PK1 cells and polysulfone hollow fiber cartridges. Water and Na ion transport function was high, and BUN and creatinine passage was recognized in these bioartificial tubules. BUN and creatinine concentrations of reabsorption fluid in these bioartificial tubules were significantly lower than those concentrations of control media and of noncell attached polysulfone hollow fiber cartridges. Though LLC-PK1 cells were more preferable cells for the use of bioartificial tubules in terms of water and electrolyte transport, the passage of BUN and creatinine was not appropriate for clinical use. To select more preferable cells for bioartificial tubules which transport water and electrolytes and do not induce passage of uremic toxins is necessary.

Animals↗

Fine structure of the retino-optic nerve junction in the chicken.

The aim of this study is to investigate a fine structure of the retino-optic nerve junction in the chicken. We especially focused on the myelin sheaths and astrocytes in the intraocular optic nerve (ION) and its adjoining parts. A part of the axons of retinal nerve fiber layer (NFL) were myelinated. Ganglion cell axons were ensheathed by loose myelin in the NFL and by a compact one in the ION and optic nerve (ON). Myelin structure changed from loose type to a compact one within the very narrow NFL-ION junction. Loose myelin forming cells are dark type of oligodendrocytes in the retina. From the most peripheral ON to the choroidal part of ION, astrocytes contained abundant microtubules. The optic nerve around the lamina cribrosa is exposed to mechanical force during eye movement. It is suggested that these microtubules may perform the cytoskeletal function. Astrocytes in the retinal part of ION had longer processes filled with abundant gliofilaments. They may provide the mechanical support for the ganglion cell axons, which are exposed directly to intraocular pressure. Although astrocytes in the retinal level of ION extended their processes into the retina, their soma was never found in the retina.

Animals↗

Chromatic variation of the abundance of PSII complexes observed with the red alga Prophyridium cruentum.

Chromatic regulation of photosystem stoichiometry in cyanophytes, green algae and probably vascular plants is achieved by regulation of the abundance of PSI in response to thylakoid electron transport state at least under our experimental conditions [cf. Fujita (1997) Photosyn. Res. 53: 83]. However, variation of not only PSI but also PSII, in reverse of each other, is characteristic of the stoichiometry regulation in red algae and some of marine cyanophytes. Our previous study with the red alga Porphyridium cruentum has revealed that PSII is inactivated by 50% upon a light shift from the light absorbed by Chl a, PSI light, to that mainly absorbed by phycobilisomes (PBS), PSII light [Fujita (1999) Plant Cell Physiol. 40: 924]. To evaluate the contribution of the photoinactivation to the chromatic variation of PSII, variation of the abundance of PSI, PSII and PBS, together with the fluorescence parameter and the activity of PSII, was followed after a light shift from PSI light to PSII light. Upon a light shift to PSII light, PSII, determined as Cyt b(559) per PBS, decreased rapidly, following the photoinactivation, down to the level a half of that before the light shift, and remained constant. Since the increase in PBS was not significant during this period, a rapid decrease of PSII/PBS led us to tentatively conclude that the degradation of PSII is a main cause for variation of the abundance of PSII. Photoinactivation of PSII, and also decrease in Cyt b(559), was accelerated, but only slightly, by the addition of chloramphenicol (CAP) at a moderate concentration while CAP at the same concentration significantly suppressed the increment of PSI determined as P700. A selective effect of CAP supports the above conclusion.

Chloramphenicol↗

Mutation of an arginine biosynthesis gene causes reduced pathogenicity in Fusarium oxysporum f. sp. melonis.

Restriction enzyme-mediated integration (REMI) mutagenesis was used to tag genes required for pathogenicity of Fusarium oxysporum f. sp. melonis. Of the 1,129 REMI transformants tested, 13 showed reduced pathogenicity on susceptible melon cultivars. One of the mutants, FMMP95-1, was an arginine auxotroph. Structural analysis of the tagged site in FMMP95-1 identified a gene, designated ARG1, which possibly encodes argininosuccinate lyase, catalyzing the last step for arginine biosynthesis. Complementation of FMMP95-1 with the ARG1 gene caused a recovery in pathogenicity, indicating that arginine auxotrophic mutation causes reduced pathogenicity in this pathogen.

Arginine↗

Surface ultrastructure of collagen fibrils and their association with proteoglycans in human cornea and sclera by atomic force microscopy and energy-filtering transmission electron microscopy.

PURPOSE: We aimed to investigate the possible association of proteoglycans with D-periodic collagen fibrils in the human cornea and sclera, using energy-filtering transmission electron microscopy (EF-TEM) and atomic force microscopy (AFM). METHODS: Human cornea and sclera were digested with keratanase to eliminate keratan sulfate proteoglycans (KSPGs). For EF-TEM observation, surface proteoglycans were detected by cupromeronic blue (CB) staining. For AFM observation, cornea and sclera were treated with sodium hydroxide before and after keratanase digestion, and the surface topology of collagen fibrils was analyzed. RESULTS: With CB staining, numerous CB-positive short filaments of surface proteoglycans (proteoglycan filaments) were observed in the interfibrillar spaces of cornea and sclera associated with collagen fibrils. AFM imaging showed that the depth and periodicity of D-periodic collagen fibrils in keratanase-treated corneal collagens were deeper and more regular than in untreated ones. Moreover, the depth and periodicity of keratanase-untreated corneal collagens were shallow and irregular in comparison with keratanase-untreated scleral collagens. On the other hand, there was no difference in depth or regularity between keratanase-treated and -untreated scleral collagen fibrils. Using AFM imaging, additional thin grooves sub-bands were detected on the surface of keratanase-treated corneal collagen fibrils. The grooves were not detected in keratanase-untreated collagen fibrils nor in scleral collagen fibrils with or without keratanase digestion. Comparing densitometry waves, the grooves of D-periodic corneal collagen sub-bands corresponded to a and c bands. CONCLUSION: Using AFM and EF-TEM to study corneal and scleral collagen fibrils and their association with proteoglycans, we conclude that KSPG is found in ample amounts in the human cornea in comparison with sclera. Moreover, we topologically detected KSPG attached to a and c bands of collagen fibrils.

Aged↗

Octreotide for severe acute bleeding from portal hypertensive colopathy: a case report.

A 56-year-old man developed severe lower gastrointestinal bleeding. He was classified as Child-Pugh grade C. Colonoscopy revealed multiple angiodysplasia-like lesions and mucosal friability throughout the entire colon (portal hypertensive colopathy, PHC). Haemostasis was immediately achieved with octreotide treatment, although melaena recurred after discontinuation of the infusion. Propranolol treatment before discontinuation of octreotide infusin prevented the recurrence of bleeding from PHC. Octreotide is a safe and effective treatment for severe acute bleeding from PHC, especially if the patient is not a candidate for transjugular intrahepatic portosystemic shunt (TIPS) or treatment with a beta-blocker due to the severity of liver disease or haemodynamic instability. However, a sufficient reduction of portal pressure by propranolol or other medical treatment may be needed in order to discontinue octreotide infusion without the recurrence of bleeding.

Acute Disease↗

Relationship between esophageal dysfunction and neuropathy in diabetic patients.

OBJECTIVE: Few studies have compared esophageal dysfunction with diabetic neuropathy, and their relationship is not yet clear. The aim of this study was to investigate the relationship between esophageal function and diabetic neuropathy. METHODS: A total of 59 patients with type 2 diabetes were studied. Long-term ambulatory esophageal pH and motility monitoring were performed. The motor nerve conduction velocity (MCV) and coefficient of variation of R-R intervals (CVRR) were also examined. RESULTS: The 59 patients were classified into four groups: group 1 consisted of patients with both diabetic autonomic neuropathy (DAN) and diabetic motor neuropathy (DMN), group 2 had DMN alone, group 3 had DAN alone, and group 4 had neither DAN nor DMN. In pH monitoring, differences were observed among the four groups in DeMeester score, total number of acid reflux episodes, and % time pH < 4 (p < 0.05). A correlation was observed between % time pH < 4 and MCV; however, no correlation with CVRR was observed. In motility monitoring, differences were observed among the four groups in amplitude of peristaltic waves (p < 0.001), rising velocity of peristaltic waves (p < 0.01), and percentage of effective peristalsis (p < 0.01). A correlation was observed between esophageal motility and MCV; however, no correlation with CVRR was observed. CONCLUSIONS: Esophageal motility disorder and abnormal acid reflux were related to DMN in diabetic patients. A significant correlation was found between esophageal dysfunction and MCV. However, no significant correlation was found between esophageal dysfunction and CVRR.

Aged↗

Involvement of two distinct catabolite-responsive elements in catabolite repression of the Bacillus subtilis myo-inositol (iol) operon.

The Bacillus subtilis inositol operon (iolABCDEFGHIJ) is involved in myo-inositol catabolism. Glucose repression of the iol operon induced by inositol is exerted through catabolite repression mediated by CcpA and the iol induction system mediated by IolR. In this study, we identified two iol catabolite-responsive elements (cre's), to which CcpA complexed with P-Ser-HPr or P-Ser-Crh probably binds. One is located in iolB (cre-iolB, nucleotides +2397 to +2411; +1 is the transcription initiation nucleotide), which was the only cre-iol found in the previous cre search of the B. subtilis genome using a query sequence of WTGNAANCGNWNNCW (W stands for A or T, and N stands for any base). Deletion and base substitution analysis of the iol region indicated that cre-iolB functions even if it is located far downstream of the iol promoter. Further deletion and base substitution analysis revealed another cre located between the iol promoter and the iolA gene (cre-iiolA, nucleotides +86 to +100); the prefix "i" indicates a location in the intergenic region. Both cre-iiolA and cre-iolB appeared to be recognized to almost the same extent by CcpA complexed with either P-Ser-HPr or P-Ser-Crh. Sequence alignment of the six known cre's, including cre-iiolA, which were not revealed in the previous cre search, exhibited another consensus sequence of WTGAAARCGYTTWWN (R stands for A or G, and Y stands for C or T); the right two thymines (TT) were found to be essential for the function of cre-iiolA by means of base substitution analysis. A cre search with this query sequence led to the finding of 14 additional putative cre's.

Bacillus subtilis↗

Comprehensive DNA microarray analysis of Bacillus subtilis two-component regulatory systems.

It has recently been shown through DNA microarray analysis of Bacillus subtilis two-component regulatory systems (DegS-DegU, ComP-ComA, and PhoR-PhoP) that overproduction of a response regulator of the two-component systems in the background of a deficiency of its cognate sensor kinase affects the regulation of genes, including its target ones. The genome-wide effect on gene expression caused by the overproduction was revealed by DNA microarray analysis. In the present work, we newly analyzed 24 two-component systems by means of this strategy, leaving out 8 systems to which it was unlikely to be applicable. This analysis revealed various target gene candidates for these two-component systems. It is especially notable that interesting interactions appeared to take place between several two-component systems. Moreover, the probable functions of some unknown two-component systems were deduced from the list of their target gene candidates. This work is heuristic but provides valuable information for further study toward a comprehensive understanding of the B. subtilis two-component regulatory systems. The DNA microarray data obtained in this work are available at the KEGG Expression Database website (http://www.genome.ad.jp/kegg/expression).

Bacillus subtilis↗