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Biomedical subjects

Akihiro Nakamura

Publications and source records attributed to Akihiro Nakamura.

At least 19 recordsLinked to original sources

Addition of pectin and soy soluble polysaccharide affects the particle size distribution of casein suspensions prepared from acidified skim milk.

Pectins are negatively charged polysaccharides employed as stabilizers in acidified milk dispersions, where caseins aggregate because of the low pH and serum separation needs to be prevented. The objective of this research was to study the effect of charge on the stabilizing functionality of the polysaccharide in acid milk drinks. Unstandardized pectins with various charges (as degree of esterification, DE) as well as soybean soluble polysaccharide (SSPS) were tested for their stabilizing behavior as a function of pH and concentration. Skim milk was acidified by glucono-delta-lactone and then homogenized in the presence of polysaccharide at different pH values (in the range from 4.2 to 3.0). Measurements of particle size distribution demonstrated that pectins with a DE of 71.4, 68.6, and 67.4 stabilized milk at pH > 4.0. Pectins with a lower DE (63.9%) needed a higher concentration (0.4%) at the same pH to show a monomodal distribution of particle sizes. Pectins with lower DE (<50%) did not stabilize the dispersions. Although this difference in behavior was attributed mainly to the pectin charge, the efficiency in stabilizing the casein dispersion decreased with decreasing pectin size. For example, the high methoxyl pectin (HMP) with 63.9 DE was smaller in size than the HMPs with a higher charge. Pectins showed a pH-dependent stabilization effect, as at pH < 4.0 the dispersions contained aggregates. When SSPS was used to stabilize acid milk, at pH < 4.0, it showed a better stabilization behavior than HMP. When SSPS and pectin were used in combination, the particle size distribution of the acid milk dispersion was pH-dependent, and results were similar to those for samples containing pectin alone. This suggested that in the mixture, pectin dominated the behavior over SSPS, even when an excess of SSPS was added to the dispersions before homogenization.

Animals↗

Stabilizing behavior of soy soluble polysaccharide or high methoxyl pectin in soy protein isolate emulsions at low pH.

The stability of emulsions prepared with soy protein isolates was investigated as a function of pH in the presence of two negatively charged polysaccharides: high methoxyl pectin (HMP) and soy soluble polysaccharide (SSPS). Both polysaccharides are composed of a backbone which contains galacturonic acid but, when added to soy protein isolate-stabilized emulsions, SSPS showed a different behavior than that of HMP. At neutral pH and above a critical concentration of stabilizer (0.05%), HMP caused flocculation of the emulsion droplets via a depletion mechanism. On the other hand, the emulsions containing a similar amount of SSPS did not show creaming or flocculation. At acidic pH (<4.0) the addition of pectin caused extensive droplet aggregation, while no aggregation was observed with the addition of SSPS. The differences in the stabilization behavior between the two polysaccharides can be attributed to their differences in charge, neutral sugars side chains, and molecular weight.

Drug Stability↗

Factors affecting survival after bronchoplasty and broncho-angioplasty for lung cancer: single institutional review of 147 patients.

OBJECTIVE: We compared the results of bronchoplasty and bronchoplasty with pulmonary angioplasty (broncho-angioplasty). Multivariate analysis was done to determine potential prognostic factors for both procedures based on our 20-year single-center experience. METHODS: Between January 1985 and December 2004, 163 bronchoplastic procedures were done in 1405 patients who underwent lung resections for lung cancer at Nagasaki University Hospital. After excluding 16 carino-plasty patients, 147 patients (118 bronchoplasty and 29 broncho-angioplasty) were included. RESULTS: In the bronchoplasty group, the postoperative morbidity was 22.9% (27/118) and the 90-day postoperative mortality was 5.9% (7/118), while in the broncho-angioplasty group the postoperative morbidity was 27.6% (8/29) and the postoperative mortality was 17.2% (5/29). The 5-year survival for all patients was 56.0%. Among patients with stage I or II, the 5-year survival was 76.2% in the bronchoplasty group and 51.9% in the broncho-angioplasty group (p=0.1791). On the other hand, among patients with stage III or IV, 5-year survival was 43.5% in the bronchoplasty group and 7.9% in the broncho-angioplasty group (p=0.0192). Multivariate analysis indicated that the type of operation, postoperative complications, histologic type, and pN status were significant factors affecting survival. CONCLUSIONS: Both bronchoplasty and broncho-angioplasty are useful for the treatment of patients with lung cancer and should be performed in stage I or II. However, careful patient selection is mandatory in patients with advanced tumor stages and in those with nonsquamous cell carcinoma, especially if broncho-angioplasty is being considered.

Adolescent↗

VEGF 164 gene transfer by electroporation improves diabetic sensory neuropathy in mice.

BACKGROUND: Diabetic neuropathy is the most common cause of peripheral neuropathy and a serious complication of diabetes. Vascular endothelial growth factor (VEGF) stimulates angiogenesis and has neurotrophic and neuroprotective activities. To examine the efficiency of VEGF 164 electro-gene therapy for neuropathy, intramuscular VEGF 164 gene transfer by electroporation was performed to treat sensory neuropathy in diabetic mice. METHODS: VEGF 164 was overexpressed in the tibial anterior (TA) muscles of streptozotocin-induced diabetic mice with hypoalgesia, using a VEGF 164 plasmid injection with electroporation. From 2 weeks after electro-gene transfer, the nociceptive threshold was measured weekly using the paw-pressure test. The TA muscles, sciatic nerve, liver and spleen were histochemically examined at 4 weeks after electro-gene transfer. RESULTS: Two weeks after electro-gene transfer into the bilateral TA muscles, the elevated nociceptive threshold was decreased to a normal level in all treated mice. Improvement of the hypoalgesia continued for 14 weeks. When the VEGF 164 plasmid was injected with electroporation into a unilateral TA muscle, recovery from hypoalgesia was observed in not only the ipsilateral hindpaw, but also the contralateral one, suggesting that VEGF circulates in the blood. No increase in the number of endoneurial vessels in the sciatic nerve was found in the VEGF 164 plasmid-electroporated mice. CONCLUSIONS: These findings suggest that VEGF 164 electro-gene therapy completely recovered the sensory deficits, i.e. hypoalgesia, in the diabetic mice through mechanisms other than angiogenesis in the endoneurium of the peripheral nerve, and may be useful for treatment for diabetic sensory neuropathy in human subjects.

Animals↗

Limited lung resection using the potassium-titanyl-phosphate laser.

BACKGROUND AND OBJECTIVES: Recently, the use of the potassium-titanyl-phosphate (KTP) laser with a wavelength of 532 nm, which is half the wavelength of the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser, has been expanding in many fields, since this laser offers hemostasis and vaporization with minimal coagulation of the underlying structures. The purpose of this study was to determine the usefulness of the KTP laser in limited lung resection done for pulmonary nodular lesions. STUDY DESIGN/PATIENTS AND METHODS: We used the KTP laser to manage 10 partial resections (Group 1) and 16 segmentectomies (Group 2). The variables that were used to compare the two methods of resection included intra-operative blood loss, mean drainage time, and post-operative morbidity. RESULTS: The mean intra-operative blood loss was smaller in Group 1 (152.8 +/- 65.0 cc, P = 0.002) than in Group 2 (341.9 +/- 178.6 cc). Mean drainage time was shorter in Group 1 (1.8 +/- 1.0 days, P = 0.0141) than in Group 2 (3.6 +/- 2.9 days). The results of both groups with respect to hemostatic and healing effects were satisfactory. On histopathologic evaluation, the KTP laser-irradiated field tissue alteration consisted of two layers with a depth up to 2 mm. CONCLUSIONS: The results of this study suggest that the KTP laser has the potential to become a useful and reliable tool for limited lung resection.

Aged↗

Video-assisted thoracic surgery lobectomy reduces the morbidity after surgery for stage I non-small cell lung cancer.

OBJECTIVE: We conducted this study to evaluate the surgical invasiveness and the safety of video-assisted thoracic surgery lobectomy for stage I lung cancer. METHODS: Video-assisted thoracic surgery lobectomies were performed on 43 patients with clinical stage IA non-small cell lung cancer. We compared the surgical invasiveness parameters with 42 patients who underwent lobectomy by conventional thoracotomy. RESULTS: Intraoperative blood loss was significantly less than that in the conventional thoracotomy group (151+/-149 vs. 362+/-321 g, p<0.01). Chest tube duration (3.0+/-2.1 vs. 3.9+/-1.9 days) was significantly shorter than those in the conventional thoracotomy group (p<0.05). The visual analog scale which was evaluated as postoperative pain level on postoperative day 7, maximum white blood count and C-reactive protein level were significantly lower than those in the conventional thoracotomy group (p<0.05). The morbidity rate was significantly lower than that in the conventional thoracotomy group (25.6% vs. 47.6%, p<0.05). Sputum retention and arrhythmia were significantly less frequent than in the conventional thoracotomy group (p<0.05). We experienced no operative deaths in both groups. CONCLUSION: We conclude that video-assisted thoracic surgery lobectomy for stage I non-small cell lung cancer patients is a less invasive and safer procedure with a lower morbidity rate compared with lobectomy by thoracotomy.

Carcinoma, Non-Small-Cell Lung↗

Carbonyl modification in rat liver histones: decrease with age and increase by dietary restriction.

We studied carbonylation, a form of oxidative modification of proteins, of histones in rat livers. Histones H1, H2B/H2A, and H3 were significantly carbonylated but the modification was almost undetectable in H4. Contrary to the generally accepted view of increased protein carbonylation with age, the modification of histones was significantly lower in old (30-month-old) than in young (5-month-old) animals. Dietary restriction of older animals for 2 months resulted in increase in carbonylation comparable to that at the young level. These findings may have physiological implications in chromatin structure/function in aging and beneficial effects of DR by influencing transcription, replication, and/or repair activities.

Aging↗

Molecular characterisation of soybean polysaccharides: an approach by size exclusion chromatography, dynamic and static light scattering methods.

Water soluble polysaccharides from soybean (SSPS) have a pectin-like structure and are used as stabilisers in acidified beverages. Physicochemical properties such as structure, molecular weight and shape or conformation are primary factors controlling their functional properties. Two soybean polysaccharides, a native SSPS and a modified SSPS treated with beta-(1-->4)-D-galactosidase (GPase/SSPS) were studied by dynamic and static light scattering (DLS, SLS) and size exclusion chromatography (SEC). Consecutive filtrations using a range of membrane pore size removed a small fraction of macromolecular aggregates from dilute polysaccharide solutions with relatively little effect on the major component molecules as monitored by DLS and SEC measurements. Access to aggregate-free dilute solutions of SSPS and GPase/SSPS allowed the direct measurement of molecular characteristics. SLS results showed that SSPS had a weight average molecular weight of (645+/-11)x 10(3)g/mol and a radius of gyration, Rg, of (23.5+/-2.8)nm. By comparing R(g) with the hydrodynamic radius, Rh (21.1+/-0.5 nm) obtained from DLS, the structural parameter rho (Rg/Rh) was found to be 1.1, suggesting that SSPS has an overall globular shape due to a highly branched structure. The modified SSPS had a significantly lower molecular weight (287+/-18)x 10(3)g/mol but a similar radius of gyration (23.2+/-1.7 nm). The structure parameter rho of GPase/SSPS was higher (rho=1.3) because of a smaller hydrodynamic radius (17.7+/-1.8 nm). This suggests that GPase/SSPS has a much less branched structure yet still differs significantly from a linear random coil conformation (rho=1.7-2.0). The results derived from SLS and DLS are in agreement with the conclusions obtained from a chemical analysis where the reduction of molecular weight of GPase/SSPS was caused by the cleavage of galactan side chains.

Carbohydrates↗

Phase-specific central regulatory systems of hibernation in Syrian hamsters.

The central body temperature (T(b)) regulation system during hibernation was investigated in Syrian hamsters of either sex. Hibernation induced in Syrian hamsters by housing them in a cold room under short day-light/dark cycle was confirmed by marked reductions in the heart rate, T(b) and respiratory rate. The hibernation of hamsters was classified into (i) entrance, (ii) maintenance and (iii) arousal phases according to T(b) changes. In hibernating hamsters, T(b) elevations were phase-selectively elicited by intracerebroventricular (ICV) injection of 8-cyclopenthyltheophylline (CPT; a selective A1-adenosine receptor antagonist) and naloxone (a non-selective opioid receptor antagonist) during the entrance and maintenance phases, respectively. Moreover, a similar T(b) elevation tendency during the maintenance phase was also induced by ICV naloxonazine, (a selective mu1-opioid receptor antagonist), although such was not the case for naltrindole (a selective delta-opioid receptor antagonist) or nor-binaltorphimine (nor-BNI, a selective kappa-opioid receptor antagonist). Furthermore, T(b) elevations in hibernating hamsters were similarly induced with ICV thyrotropin-releasing hormone (TRH) during the entrance and maintenance phases. Furthermore, ICV injection of the anti-TRH antibody ameliorated the T(b) elevations induced by tactile stimulation. These results suggest that activation of the A1-receptor by adenosine is important for the generation of hypothermia in the entrance phase, and that activation of the mu1-opioid receptor by opioid peptides is required for perpetuation of hypothermia in the maintenance phase. In addition, TRH is a key endogenous substance involved in T(b) elevations during the arousal phase of hibernating hamsters.

Adenosine↗

Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, reduces the progression of experimental osteoarthritis in guinea pigs.

OBJECTIVE: To evaluate the in vivo therapeutic effect of pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, on the development of lesions in a guinea pig model of osteoarthritis (OA), and to determine the influence of pioglitazone on the synthesis of matrix metalloproteinase 13 (MMP-13) and interleukin-1beta (IL-1beta) in articular cartilage. METHODS: The OA model was created by partial medial meniscectomy of the right knee joint. The guinea pigs were divided into 4 treatment groups: unoperated animals that received no treatment (normal), operated animals (OA guinea pigs) that received placebo, OA guinea pigs that received oral pioglitazone at 2 mg/kg/day, and OA guinea pigs that received oral pioglitazone at 20 mg/kg/day. The animals began receiving medication 1 day after surgery and were killed 4 weeks later. Macroscopic and histologic analyses were performed on the cartilage. The levels of MMP-13 and IL-1beta in OA cartilage chondrocytes were evaluated by immunohistochemistry. RESULTS: OA guinea pigs treated with the highest dosages of pioglitazone showed a significant decrease, compared with the OA placebo group, in the surface area (size) and grade (depth) of cartilage macroscopic lesions on the tibial plateaus. The histologic severity of cartilage lesions was also reduced. A significantly higher percentage of chondrocytes in the middle and deep layers stained positive for MMP-13 and IL-1beta in cartilage from placebo-treated OA guinea pigs compared with normal controls. Guinea pigs treated with the highest dosage of pioglitazone demonstrated a significant reduction in the levels of both MMP-13 and IL-1beta in OA cartilage. CONCLUSION: This is the first in vivo study demonstrating that a PPARgamma agonist, pioglitazone, could reduce the severity of experimental OA. This effect was associated with a reduction in the levels of MMP-13 and IL-1beta, which are known to play an important role in the pathophysiology of OA lesions.

Administration, Oral↗

Primary screening of relatively less allergenic wheat varieties.

Since the number of wheat-allergic patients has been increasing in recent years, less allergenic wheat varieties are socially demanded. The aim of this study was to primarily screen 324 varieties of wheat picked up from various parts of the world. Prior to the screening, the inhibition ELISA (enzyme-linked immunosorbent assay) was examined with major wheat allergens (glutenin, gliadin and alpha-amylase inhibitor). As a result, the patient's IgE antibodies used in this assay reacted to these three allergens, and thereby turned out to be suitable for the primary screening for the less allergenic wheat varieties. Thus, the allergenicity of each wheat sample was measured by direct ELISA using the sole patient's serum as an IgE source and 'Aoba Komugi' as a control (a value of 1.0). The mean +/- SD of all kinds was 1.14 +/- 0.37. Among them, 'CM32859' (Mexico) gave the lowest value (0.38). Several other varieties, such as 'Einkorn' (Unknown), 'Iliniaza' (Ecuador), 'Hsin Mai 2' (China), 'Italy 1' (Italy) and so on, also serve as candidates for the less allergenic varieties. More detailed secondary screening will lead to a finding of the less allergenic wheat varieties for wheat-allergic patients, because these varieties are expected to become mother plants for breeding.

Allergens↗

[Perioperative management of extended surgery for advanced lung cancer].

Extended surgery for advanced non-small cell lung cancer includes combined resection of T3 or T4 organs and extended lymph node dissection in N2 or N3 cases. It is well known that the incidence of complications with extended surgery is higher in comparison with standard surgery due to the greater extent of invasiveness of the former. The management of extended surgery patients requires an understanding of the characteristic complications and their frequency for each type of surgery. Perioperative management including an accurate preoperative diagnosis and the prevention of postoperative complications affects prognosis because mortality rate is higher in patients in whom more complications occur.

Carcinoma, Non-Small-Cell Lung↗

Study of the role of the carbohydrate and protein moieties of soy soluble polysaccharides in their emulsifying properties.

The objective of this work was to investigate the role played by the protein fraction of soy soluble polysaccharide (SSPS) during its adsorption at oil/water interfaces. SSPS was separated in a high (HMF; 310 kDa) and low (LMF; 20 kDa) molecular weight fraction by gel filtration. SSPS/HMF consisted of 91.6% carbohydrate and 2.2% protein and showed better emulsifying properties than those of the whole SSPS, whereas SSPS/LMF seemed to affect negatively the adsorption behavior of SSPS. SDS-PAGE of the protein fraction obtained from SSPS/HMF showed a molecular mass of 50 kDa, was composed predominantly of proline (23.1%) and glutamic acid (15.2%), and still contained 8.8% of neutral sugar and 5.3% of uronic acid. Results indicated that not all of the protein material present in SSPS contributes to SSPS functionality but that only the material associated with HMF aids in the adsorption of SSPS onto oil/water interfaces.

Adsorption↗

Regulation of amphiphysin1 by mitogen-activated protein kinase: its significance in nerve growth factor receptor-mediated endocytosis.

Amphiphysin1, which can simultaneously bind to dynamin1 and the clathrin adaptor AP-2, is essential for dynamin1 recruitment during receptor-mediated endocytosis, but little is known about its regulatory mechanism. Here, we purified a 120-kDa mitogen-activated protein kinase (MAPK) substrate protein from porcine brains and identified the protein as amphiphysin1. Serine phosphorylation of amphiphysin1 was rapidly induced by nerve growth factor (NGF) in PC12 cells, and the induction was blocked by a MAPK inhibitor. Furthermore, when phosphorylated by MAPK in vitro or by NGF treatment in vivo, amphiphysin1 failed to bind to AP-2, but its association with dynamin1 was unaffected. Consistent with this, mutation of consensus MAPK phosphorylation sites increased amphiphysin1 binding to AP-2 and their intracellular colocalization. Thus, we propose that MAPK phosphorylation of amphiphysin1 controls NGF receptor/TrkA-mediated endocytosis by terminating the amphiphysin1-AP-2 interaction. This perhaps helps to regulate the availability of amphiphysin1-dynamin1 complexes for binding to the endocytic vesicle.

Adaptor Protein Complex 2↗

Role of gamma delta T cells in the inflammatory response of experimental colitis mice.

We examined the severity of experimental colitis induced by dextran sulfate sodium (DSS) using immunologically manipulated mice. C57BL/6 mice showed more severe colitis than BALB/c mice, but mice of both strains recovered fully from the disease after the removal of DSS from their drinking water. The infiltrated cells at the lesions were mainly granulocytes in normal littermates. However, C.B-17 scid, IL-7Ralpha deficient, and TCR-Cbetadelta double-deficient mice showed severe colitis and did not recover from the disease even after the removal of DSS. It was found that the infiltrated cells at the lesions in the lethal strains were monocytes. Although both TCR-Cdelta(-/-) and TCR-Cbeta(-/-) mice showed severe colitis phenotypes, infiltration in the former is monocyte-dominant while that in the latter is granulocyte-dominant. Thus the type of cells that infiltrate at the lesions of DSS-induced experimental colitis may be controlled by functional T cell subsets. Immunohistological and RT-PCR analyses of the inflamed colon revealed that the murine homologue of human GROalpha released by some cells under the control of gammadeltaT cells is a possible candidate determining the severity of DSS-induced experimental colitis.

Animals↗

Expression of DNA (5-cytosin)-methyltransferases (DNMTs) in hepatocellular carcinomas.

Down-regulation of tumor suppressor genes by hypermethylation of 5'-CpGs is one of the important mechanisms involved in tumor development. DNA (5-cytosine)-methyltransferases (DNMTs) are enzymes that methylate the cytosine residue of CpGs, and four types have been identified (DNMT1, 2, 3a and 3b). To examine the involvement of DNMTs in hepatocellular carcinogenesis, we measured DNMT mRNAs in hepatocellular carcinomas (HCCs). mRNAs of DNMT1, 2, 3a and 3b were detected by reverse transcription-PCR analysis and quantified by a real-time PCR method in surgically resected HCCs and adjacent non-tumorous liver tissue. DNMT1 was expressed in all tissues and at a significantly higher level in HCCs than in non-tumorous liver tissue (P=0.01). DNMT2 was expressed at a low level in all tissues. DNMT3a and DNMT3b mRNA were undetectable in normal liver. DNMT3a was expressed in all HCCs and was expressed at similar levels in 60% of the non-tumorous liver tissues. DNMT3b mRNA was detected at a significantly higher level (P=0.002) in HCCs than in non-tumorous liver tissues. The amount of DNMT1, 3a and 3b mRNA was not different between HCCs with or without hypermethylation of the CDH1 promoter. These data suggest that overexpression of DNMT1 and DNMT3b contributes to hepatocellular carcinogenesis.

Journal Article↗