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Biomedical subjects

A Kitagawa

Publications and source records attributed to A Kitagawa.

At least 19 recordsLinked to original sources
PubMed2006

Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

Animals↗
PubMed2006

New nanotechnology for the guided tissue regeneration of skin--potential of lyotropic liquid crystals.

Tissue in body must quickly recognize injury to response to the rapid pace of epidermal growth. In skin, the epidermal cells must also react to danger signals from the surrounding extracellular lipid of the stratum corneum spaces and immediately participate by initiating the wound repair process. The topical administration of the lyotropic liquid crystal nanocube to stratum corneum rapidly broke down the lipid lamella structure which would be recognized as a wound without organ-change. This can activate a variety of biological processes. This study set out to determine whether the phase transition of the lipid to a neighbouring different physicochemical structure can stimulate keratinocyte cells and what mechanism is responsible for this response. Using small angle x-ray scattering (SAXS) analysis, a response to the transient structural change of lipid was detected which might result from the diffusion of oil and/or water from nanocube liquid crystal towards the lipid lamella phase. Simultaneously, a significant increase in growth factors and inflammatory cytokines was detected after administration of nanocube. Not only the excess expression of cytokines but also the extent of TEWL as a barrier marker of skin increased. These observations suggest that a structural change in lipid can stimulate and trigger recognition of a slight injury in the wound defence and a repair response as homeostasis. This method actually succeeded in improving photo-induced hyperpigmentation on a human face.

Animals↗
PubMed2006

Enhanced skin regeneration by nanoegg formulation of all-trans retinoic acid.

All-trans retinoic acid (atRA) which could smooth wrinkles and produce less pigmented skin after a few months of treatment has been studied in research into topical treatments for a potent inhibitor of new melanin production. However, the clinical responses of commercial atRA cream predominantly comprise severe inflammation. We report a novel nanotechnology "nanoegg" system giving improved effects of atRA self-assembly which were coated by CaCO3. Dorsal areas of hairless mouse and porcine skin were employed for administration of nanoegg ointment and commercial products. The mRNA for heparin-binding epidermal growth factor-like growth factor (HB-EGF) from tissues was measured by a real-time PCR method. All tissues were stained for detection of hyaluronate and the thickness of the epidermis. A clinical trial in humans was carried out at St. Marianna University in Japan. As a result, the irritation and inflammation associated with atRA molecules were substantially reduced. The physicochemical instability of atRA was also dramatically improved. Furthermore, nanoegg enhanced marked expression of mRNA for HB-EGF from keratinocytes, which is known as one of the markers of keratinocyte turnover. Also, production of hyaluronate was surprisingly in the intercellular spaces of the basal and spinous cell layers 2 days after treatment. Even at the low concentration of atRA in the nanoegg system, the proliferation and differentiation of keratinocyte was somewhat enhanced. A nanoegg may thus not only prevent adverse effects, but also markedly enhance the main effect.

Administration, Topical↗
PubMed2005

Anchorage on fibronectin via VLA-5 (alpha5beta1 integrin) protects rheumatoid synovial cells from Fas-induced apoptosis.

BACKGROUND: Rheumatoid synovial cells are resistant to apoptosis induction in vivo, whereas, fibroblast-like synovial cells in rheumatoid arthritis (RA-FLS) are vulnerable to Fas-induced apoptosis in vitro. OBJECTIVE: To clarify this discrepancy by studying the contribution of the interaction between cellular integrin and matrix fibronectin (Fn), which is significantly increased in the rheumatoid joints, to the induction of apoptosis in RA-FLS. METHODS: Integrin and Fas mRNAs were measured by reverse transcription-polymerase chain reaction in RA-FLS. Integrins expressed in rheumatoid synovial tissues were analysed by immunohistochemistry. RA-FLS plated either on Fn or on control poly-L-lysine were incubated with agonistic anti-Fas monoclonal antibodies (mAbs). Apoptosis induction was evaluated using terminal deoxynucleotidyl transferase mediated UTP nick end labelling (TUNEL) and immunoblotting for caspase-3 and poly (ADP-ribose) polymerase in the presence or absence of anti-VLA-5 mAb. RESULTS: VLA-5 (alpha5beta1 integrin), a major integrin expressed on RA-FLS, was required for the adhesion of RA-FLS on Fn. RA-FLS plated on Fn were more resistant to Fas-induced apoptosis than those plated on control poly-L-lysine. This protection by Fn was reversed by anti-VLA-5 mAb. CONCLUSION: Anchorage of RA-FLS on matrix Fn via VLA-5 protects RA-FLS from Fas-induced apoptosis, and Fn abundantly present in rheumatoid synovium appears to afford RA-FLS resistance against apoptosis induction in vivo.

Antibodies, Monoclonal↗
PubMed2005

Does the use of a cleanser on skin surrounding pressure ulcers in older people promote healing?

OBJECTIVE: To determine whether the use of a skin cleanser on the skin surrounding pressure ulcers helps to promote healing. METHOD: The study was conducted over a two-year period in patients with stage II or more pressure ulcers. All subjects were at least 65 years of age and resident in a long-term care hospital. During the first year, skin was cleansed with normal saline. In year two, a pH-balanced cleanser was used. The healing times for the two methods were then compared. RESULTS: Healing time was shorter in the group using the cleanser for every stage of ulcer, with an especially significant difference for stage II ulcers (p=0.002). Analysis using the Cox proportional hazards model found a 1.79-fold improvement in the healing rate of stage II ulcers when the surrounding skin was washed with the cleanser. CONCLUSION: Cleaning the surrounding skin with a cleanser rather than normal saline promotes the healing of pressure ulcers.

Aged↗
PubMed2004

The LET spectra at different penetration depths along secondary 9C and 11C beams.

Owing to the potentially therapeutic enhancement of delayed particles in treating malignant diseases by radioactive 9C-ion beam, LET spectra at different penetration depths for a 9C beam with 5% momentum spread, produced in the secondary beam line (SBL) at HIMAC, were measured with a multi-wire parallel-plate proportional counter. To compare these LET spectra with those of a therapeutic 12C beam under similar conditions, the 12C beam was replaced with an 11C beam, yielded in the SBL as well and having almost the same range as that of the 9C beam. The LET spectra of the 9C beam and its counterpart, i.e. the 11C beam, at various depths were compared, especially around the Bragg peak regions. The results show that nearby the Bragg peak lower LET components decreased in the LET spectra of the 9C beam while extra components between the LET peak caused by the primary beam and the lower components due to the fragments could be observed. These additional contributions in the LET spectra could be attributed to parts of the emitted particles from the radioactive 9C ions with suitable conditions regarding the LET counter. Integrating these LET spectra in different manners, depth-dose and dose-averaged LET distributions were obtained for the 9C and 11C beams, forming the basic data sets for further studies. In general, the depth-dose distributions of the 9C and 11C beams are comparative, i.e. almost the same peak-to-plateau ratio. The ratio for the 9C beam, however, has room to increase due to the geometric structure limitation of the present detector. The dose-averaged LETs along the beam penetration are always lower for the 9C beam than for the 11C beam except at the falloff region beyond the Bragg peak. Applying the present depth-dose and dose-averaged LET data sets as well as the essential radiobiological parameters obtained with 12C beams previously for HSG cells, an estimate concerning the HSG cell surviving effects along the penetration of the 9C and 11C beams shows that lower survival fractions for the 9C beam at the distal part of the Bragg peak, corresponding to the stopping region of the incoming 9C ions, can be expected when the same entrance dose is given. It is still hard to appreciate the potential of 9C beams in cancer therapy based on the present LET spectrum measurement, but it provides a substantial basis for upcoming radiobiological experiments.

Calibration↗
PubMed2004

A single treatment with microcapsules containing a CXCR4 antagonist suppresses pulmonary metastasis of murine melanoma.

Biodegradable poly D,L-lactic acid (PLA, molecular weight: ca. 5000) microcapsules containing a CXCR4 antagonist (4F-benzoyl-TE14011) were prepared (4F-benzoyl-TE14011-PLA), and their anti-metastatic activity was evaluated in mice. A single subcutaneous administration of 4F-benzoyl-TE14011-PLA significantly reduced the number of colonies formed by pulmonary metastasis of B16-BL6 melanoma cells expressing CXCR4. The same dose of 4F-benzoyl-TE14011 in a single or a series of treatments affected little. The substance 4F-benzoyl-TE14011 dose-dependently suppressed B16-BL6 cell growth. In the cells cultured with SDF-1, a more potent suppression was observed. 4F-Benzoyl-TE14011 was rapidly released from 4F-benzoyl-TE14011-PLA for an initial period, both in vitro and in vivo. A steady release was thereafter observed. Therefore, this drug release profile might contribute to prevention of melanoma metastasis at the steps involving the migration and cell growth. These results also show that a sustained drug release formulation could be a useful drug delivery system for CXCR4 antagonists.

Animals↗
PubMed2004

Reliability and validity of DESIGN, a tool that classifies pressure ulcer severity and monitors healing.

OBJECTIVE: This study reviews the validity and reliability of DESIGN, a tool for classifying pressure ulcer severity and monitoring progression towards healing. Only the tool's healing progression component was evaluated. METHOD: Inter-rater reliability was evaluated by calculating the agreement rate of scores, based on eight photos of pressure ulcers and six actual ulcers, made by a panel of seven nurses. Validity was assessed, using the same eight photos, by comparing DESIGN scores with those made using the validated Pressure Sore Status Tool (PSST). RESULTS: The DESIGN inter-rater reliability results showed a high correlation of r = 0.98 for the photos and r = 0.91 for the real-life patients with pressure ulcers, respectively, for all seven raters based on total scores. For validity, a correlation greater than 0.91 was found between the DESIGN and PSST scores. CONCLUSION: Based on our results, DESIGN was found to have both high inter-rater reliability and high validity among the seven nurses who quantitatively evaluated the wound-healing progress of the pressure ulcers in this study.

Humans↗
PubMed2003

Washout measurement of radioisotope implanted by radioactive beams in the rabbit.

Washout of 10C and 11C implanted by radioactive beams in brain and thigh muscle of rabbits was studied. The biological washout effect in a living body is important in the range verification system or three-dimensional volume imaging in heavy ion therapy. Positron emitter beams were implanted in the rabbit and the annihilation gamma-rays were measured by an in situ positron camera which consisted of a pair of scintillation cameras set on either side of the target. The ROI (region of interest) was set as a two-dimensional position distribution and the time-activity curve of the ROI was measured. Experiments were done under two conditions: live and dead. By comparing the two sets of measurement data, it was deduced that there are at least three components in the washout process. Time-activity curves of both brain and thigh muscle were clearly explained by the three-component model analysis. The three components ratios (and washout half-lives) were 35% (2.0 s), 30% (140 s) and 35% (10 191 s) for brain and 30% (10 s), 19% (195 s) and 52% (3175 s) for thigh muscle. The washout effect must be taken into account for the verification of treatment plans by means of positron camera measurements.

Animals↗
PubMed2003

Washout studies of 11C in rabbit thigh muscle implanted by secondary beams of HIMAC.

Heavy ion therapy has two definite advantages: good dose localization and higher biological effect. Range calculation of the heavy ions is an important factor in treatment planning. X-ray CT numbers are used to estimate the heavy ion range by looking up values in a conversion table which relates empirically photon attenuation in tissues to particle stopping power; this is one source of uncertainty in the treatment planning. Use of positron emitting radioactive beams along with a positron emission tomograph or a positron camera gives range information and may be used as a means of checking in heavy ion treatment planning. However, the metabolism of the implanted positron emitters in a living object is unpredictable because the chemical forms of these emitters are unknown and the metabolism is dependent on the organ species and may be influenced by many factors such as blood flow rate and fluid components present. In this paper, the washout rate of 11C activity implanted by injecting energetic 11C beams into thigh muscle of a rear leg of a rabbit is presented. The washout was found to consist of two components, the shorter one was about 4.2 +/- 1.1 min and the longer one ranged from 91 to 124 min. About one third of the implanted beta+ activity can be used for imaging and the rest was washed out of the target area.

Animals↗
PubMed2002

Insulin-loaded biodegradable PLGA microcapsules: initial burst release controlled by hydrophilic additives.

We investigated the controlled release of human insulin at an initial stage from poly(DL-lactic-co-glycolic acid) (PLGA, M(w) 6600) spherical matrices. PLGA microcapsules were prepared by the novel solvent evaporation multiple emulsion process. When the crystalline insulin was dispersed in dichloromethane as solid-in-oil (S/O) dispersion, it was found that most of insulin molecules were inlaid on the surface of PLGA microcapsules. Consequently, insulin-loaded PLGA microcapsules exhibited marked rapid release of insulin within several hours in both in vivo and in vitro experiments. On the other hand, the addition of glycerol or water in the primary dichloromethane dispersion results in drastically suppressed initial release. It was found by SEM observation that water- or glycerol-in-oil (W/O or G/O) type mini-emulsion droplets with a mean diameter of 300-500 nm were formed in this primary solution. This phenomenon can be theoretically presumed to occur because insulin and PLGA molecules, having amphiphilic properties, converge on the interface between the hydrophilic additive and dichloromethane. Hence, insulin molecules heterogeneously located in the inside of PLGA microcapsules, not on the surface, would be gradually released with PLGA hydrolytic decomposition. As an additional effect of glycerol, the initial burst was further suppressed due to the decrease of the glass transition temperature of PLGA from 42.5 to 36.7 degrees C. Since the annealing of PLGA molecules took place at around 37 degrees C, the porous structure of microspheres immediately disappeared after immersion in PBS or subcutaneous administration. The insulin diffusion through the water-filled pores would be effectively prevented. The strict controlled initial release of insulin from the PLGA microsphere suggested the possibility of utilization in insulin therapy for type I diabetic patients who need construction of a basal insulin profile.

Animals↗
PubMed2001

Selection of peptides that bind to the core oligosaccharide of R-form LPS from a phage-displayed heptapeptide library.

To characterize common sites within the core oligosaccharide of the R-form lipopolysaccharide (LPS), we screened peptides from a phage-displayed heptapeptide library by using the most truncated form of R-LPS, Re-LPS (S. Typhimurium SL1165) as a ligand. After three rounds of biopanning/amplification and subsequent screening by phagemid enzyme-linked immunosorbent assay (ELISA), we selected three distinct clones that bind to the ligand LPS. We characterized the binding sites of the three clones by ELISA and thin-layer chromatography immunostaining and found that the three clones bind the two Re-LPSs (SL1165 and S. Minnesota Re595) and Rb2-LPS. In addition, one of the clones also bound to S-form LPS (S. Enteritidis). Current data show that those clones bind to common carbohydrate structure(s) expressed in the core oligosaccharides of those LPS samples.

Ligands↗
PubMed2001

Marked hypotensive and blood flow-increasing effects of a new lipo-PGE(1) (lipo-AS013) due to vascular wall targeting.

Lipo-AS013 is being developed as an improved formulation of lipo-PGE(1), which is widely used in clinical practice in Japan and some Asian countries. We have previously reported that lipo-AS013, which is a lipid microsphere (LM) preparation of a chemically stable and lipophilic PGE(1) prodrug (AS013, Fig. 1), slowly releases small amounts of the active ingredient (AS013) in human plasma. In the present study, to estimate the vascular wall targeting ability and efficacy of lipo-AS013, we determined the hypotensive and blood flow-increasing effects of lipo-AS013, lipo-PGE(1), PGE(1)CD, and AS013. Lipo-AS013 was found to have longer-lasting hypotensive and blood flow-increasing effects than the other agents. The two LM preparations, lipo-PGE(1) and lipo-AS013, had a markedly stronger effect than PGE(1)CD and AS013 alone, demonstrating the benefit of drug delivery using LM. In spontaneously hypertensive rats (SHR), lipo-AS013 also had a significant hypotensive effect. To confirm vascular wall targeting by lipo-AS013, the localization of PGE(1) in the aorta and neovascular capillaries of rat was investigated by immunostaining. The results indicated that lipo-AS013 was more efficient at delivering the active ingredient (AS013) to the vessel wall. In conclusion, lipo-AS013 could supersede lipo-PGE(1) and PGE(1)CD in clinical use.

Alprostadil↗
PubMed2001

Effects of cresols (o-, m-, and p-isomers) on the bioenergetic system in isolated rat liver mitochondria.

It is known that o-, m- and p-cresols exert a toxic effect on rat liver cells. However, there is little information on the mechanism for the hepatotoxicity of cresols. We, therefore, investigated the effects of o-, m-, and p-cresols on the bioenergetic system using isolated rat liver mitochondria. When o-, m- or p-cresol was added to liver mitochondria with glutamate or succinate at concentrations of 0.3 to 6.0 mumol/mg protein, each cresol isomer reduced the rate of state 3 respiration dose-dependently. Three cresol isomers at 6.0 mumol/mg protein each inhibited state 3 respiration in liver mitochondria with glutamate or succinate by about 60 or 20%, respectively. The three isomers affected NAD- and succinate-linked respirations in liver mitochondria, by which the respiratory control ratio was dose-dependently attenuated. The inhibitory effects of o-, m- and p-cresols on the NAD-linked respiration were stronger than those on the succinate-linked respiration. However, three cresol isomers had little effect on the P/O ratio in liver mitochondria with glutamate or succinate. Three cresol isomers at 15 mumol/mg protein each induced the swelling in the absence of Ca2+ in medium and accelerated the swelling of liver mitochondria in the presence of Ca2+ in medium. These results indicate that o-, m- and p-cresols inhibit liver mitochondrial respiration and induce or accelerate the swelling of liver mitochondria, and suggest that liver mitochondria may be one of the targets for the hepatotoxic actions of cresols.

Animals↗
PubMed2001

Investigation of coronary artery bypass grafting for a patient with myelodysplastic syndrome.

A 79-year-old male with unstable angina, who had myelodysplastic syndrome (MDS), was treated with coronary artery bypass grafting (CABG). MDS causes refractory anemia accompanied by various degrees of granulocytopenia and thrombocytopenia. Pancytopenia caused by MDS may complicate patients with major infections and bleeding during cardiac surgery. There were very few patients with MDS who had undergone open-heart surgery. Three case studies, including this study, had reported successful cases of CABG in patients with MDS and the analogous diseases of MDS. We used granulocyte colony-stimulating factor (G-CSF), red blood cells (RBCs) and platelets transfusions in peri-operative state. We did not need a large amount of transfusion of RBCs and platelets in intra-operative and postoperative states. We had prevented major bleeding and severe wound infections in the acute postoperative state.

Aged↗
PubMed1999

[Analysis of the long-term prognosis for conjunctival malignant melanomas in Japan].

PURPOSE: To investigate the long-term prognosis for primary conjunctival malignant melanomas in Japan. MATERIALS & METHODS: We conducted a survey of 61 cases which had been reported in a 38-year period (1959 to 1996). We gathered information regarding the survival of patients, the post-operative follow-up period, the causes of death, and recurrences. Answers were obtained segarding 51 cases (84%). Detailed progress was identified in 23 of these cases. The survival rates were calculated using the Kaplan-Meier method. RESULTS: The survival rates were 95.1% after 1 year, 72.9% after 3 years, and 53.4% after 5 years. These values are relatively low compared with those reported in Europe and the United States.

Adolescent↗