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Biomedical subjects

H Nakamura

Publications and source records attributed to H Nakamura.

At least 109 records · Page 6Linked to original sources

The effect of high sugar intake on the development of periradicular lesions in rats with type 2 diabetes.

Diabetes mellitus is associated with depression of natural defenses against infection and increases the risk of periodontal disease. However, the effects of diabetes on periradicular tissue, which differs structurally from periodontal tissue, are not known. In this study, we evaluated the effects of type 2 diabetes on the development of periradicular lesions after exposure of the pulp in the left mandibular first molar through the occlusal surface in rats. GK rats with spontaneous non-insulin-dependent diabetes mellitus and Wistar rats (controls) received a normal laboratory diet and either water or a 30% sucrose solution. At both 2 and 4 weeks after pulp exposure, histologic analysis showed that alveolar bone resorption was most severe and the periradicular lesions were largest in diabetic rats given the sucrose solution. These results suggest that the metabolic conditions produced by type 2 diabetes enhance the development of periradicular lesions in rats.

Alveolar Bone Loss↗

Molecular regulation of the oxytocin receptor in peripheral organs.

The oxytocin receptor belongs to the G-protein-coupled seven transmembrane receptor superfamily. Its main physiological role is regulating the contraction of uterine smooth muscle at parturition and the ejection of milk from the lactating breast. Oxytocin receptor expression is observed not only in the myometrium and mammary gland but also in the endometrium, decidua, ovary, testis, epididymis, vas deferens, thymus, heart and kidney, as well as in the brain. The expression profile shows a tissue-specific as well as a stage-specific pattern. The oxytocin receptor gene is a single-copy gene consisting of four exons and three introns, localized at 3p25-3p26.2 in the human chromosome. In transfection studies using a fusion construct containing the promoter region of the oxytocin receptor gene inserted in a reporter plasmid, neither proinflammatory cytokines nor oestrogen directly activate the gene. The nuclear fractions from up-regulated (term myometrium) and down-regulated (non-pregnant myometrium) tIssues show differential patterns of protein binding to the 5'-flanking region, and a human homologue of chicken MafF has been cloned as a term-myometrium-specific oxytocin receptor modulator. The oxytocin receptor gene appears to be highly methylated. Methylation around intron 1 and in intron 3 might contribute to tIssue-specific suppression of the gene. The oxytocin receptor is also regulated by desensitization, whose mechanism appears to involve loss of ligand-binding activity of the protein as well as suppression of the oxytocin receptor mRNA transcription. These findings taken together indicate that the oxytocin receptor is regulated in a very complicated manner, and the transcriptional regulatory elements critical for this regulation should be investigated further.

Animals↗

Effects of transdermal and oral estrogen supplementation on endothelial function, inflammation and cellular redox state.

The incidence of ischemic heart disease shows a sharp rise after menopause. However, the effects of hormone replacement therapy (HRT) on cardiovascular disease are still controversial. Not only oxidative stress, but also inflammation has been suggested to play an important role in the pathogenesis of cardiovascular events. We compared the effects of HRT on endothelial function, cellular antioxidant system and inflammation between oral and transdermal administration in mild hypercholesterolemic postmenopausal women. Transdermal estradiol replacement was administrated to 12 patients (mean age 53 years) for 12 weeks, and oral conjugated equine estrogen was administrated to 12 patients (mean age 54 years) for 12 weeks. The flow-mediated endothelium-dependent dilation of the brachial artery, serum levels of thioredoxin as a marker of the cytoprotective antioxidant system, and high-sensitivity C-reactive protein (hs-CRP) were measured every 4 weeks. The flow-mediated vasodilation increased with HRT (oral, baseline 4.9 +/- 0.5, 4-week 8.9 +/- 0.7*, 8-week 9.9 +/- 0.6*, 12-week 9.4 +/- 0.7*; transdermal, 4.7 +/- 0.6, 8.3 +/- 0.7*, 9.1 +/- 0.8*, 8.9 +/- 0.9%*, * = p < 0.01 versus baseline). The thioredoxin levels decreased with HRT (oral, 26.1 +/- 7.2, 24.1 +/- 8.2, 22.1 +/- 7.8, 19.1 +/- 7.0*; transdermal, 26.9 +/- 7.4, 23.4 +/- 8.7, 21.1 +/- 7.9, 19.2 +/- 7.2 ng/ml*, * = p < 0.01 versus baseline). There were no differences in the variation of the flow-mediated vasodilation or thioredoxin concentrations between the 2 groups. The hs-CRP levels increased with oral HRT (0.32 +/- 0.12, 0.72 +/- 0.17*, 0.86 +/- 0.23*, 0.88 +/- 0.21 mg/dl*, * = p < 0.01 versus baseline), while transdermal HRT did not elicit any changes (0.35 +/- 0.15, 0.34 +/- 0.17, 0.38 +/- 0.20, 0.36 +/- 0.22 mg/dl). The differences of hs-CRP concentrations between the 2 groups analyzed by 2-way ANOVA were significant (p < 0.01). Oral HRT instigated inflammation, but transdermal did not. Both oral and transdermal HRT, however, improved endothelial function and decreased oxidative stress through affecting the cellular redox state. These differentials in the effects caused by the course of administration may affect the future cardiovascular events.

Administration, Cutaneous↗

[Thoracoscopic resection of localized fibrous tumor of the pleura; report of a case and review of the Japanese literature].

A 61-year-old female was admitted with abnormal shadow on chest X-ray. Chest computed tomography (CT) showed a clearly localized flat tumor at the peripheral region of the left lung. We suspected localized fibrous tumor of the pleura (LFTP) and performed video-assisted thoracic surgery (VATS). Under the thoracoscopy, the tumor was connected to the visceral pleura with a short pedicle and completely resected with safety margin. Pathological findings, including immunohistochemical examination, definitely revealed benign LFTP. VATS is a good indication for the diagnosis and treatment of LFTP. This case was reported together with some reviews of the literature.

Female↗

[A resected case of malignant fibrous histiocytoma of the chest wall].

We report a 74-year-old woman with malignant fibrous histiocytoma (MFH), treated successfully by radiation and followed with chest wall resection and reconstruction. The patient suffered from right back pain and her chest X-ray showed a clear round shadow in the middle field of the right lung. Chest computed tomography (CT) showed a 5 x 5 cm tumor in diameter, involving the right 8 rib with destructive changes. After radiation therapy of total 30 Gy to the tumor to obtain the safety surgical margin, we widely resected 10 x 9 cm chest wall with 3 ribs in area under thoracoscopy and performed reconstruction using GORE-TEX Soft Tissue Patch. The pathological and immuno-histochemical diagnosis showed pleomorphic type of MFH. Final result of the tumor negative in surgical margin manifested that our technique of chest wall resection and reconstruction using thoracoscope after the irradiation to the tumor was very safe and useful.

Aged↗

[Inflammatory pseudotumor diagnosed by thoracoscopic resections; report of a case].

A 65-year-old woman was referred to our hospital because of cough and sputum. Chest CT scan revealed a coin lesion (about 1.5 cm diameter) with slight speculation at the right upper lobe. We suspected a lung cancer and performed video assisted thoracic surgery (VATS). Under the thoracoscopy, the tumor was completely extirpated with safety margin by the partial resection of the right upper lobe. Pathological findings definitely revealed inflammatory pseudotumor, fibrohistiocytic variant type. VATS is a good indication for the diagnosis and treatment of inflammatory pseudotumor. This case was reported together with some reviews of the literature.

Aged↗

Blood endothelin-1 and cold-induced vasodilation in patients with primary Raynauld's phenomenon and workers with vibration-induced white finger.

AIM: Cold water-immersion induces vasoconstriction with an elevation of blood endothelin-1, which is a potent vasoconstrictor peptide, in patients with primary Raynaud's phenomenon (PRP). However, physiological involvement of endothelin-1 in cold-induced vasodilation (CIVD) remains to be elucidated. METHODS: We monitored changes of finger blood flow during cold water (10 degrees C) immersion and assayed blood endothelin-1 in 7 PRP patients and 7 workers with vibration-induced white finger (VWF) and in the respective control subjects. RESULTS: While significant reductions in finger blood flow at 2 min after the immersion were observed in PRP patients and VWF workers, its elevation at 4 min, which was considered to reflect CIVD, was recognized only in PRP patients. In healthy controls, blood endothelin-1 increased at 4 min and returned to the basal level immediately after the immersion. The increase in blood endothelin-1 at 4 min in PRP patients was greater than that in controls, and continued even after the immersion. Conversely, the increase neither at 4 min nor after immersion was seen in VWF workers. Local vascular changes produced by repetitive vibration may be responsible for the attenuated CIVD and unchanged blood endothelin-1 during cold water-immersion in VWF workers. CONCLUSION: Our results showing elevated blood endothelin-1 during and after immersion in PRP contrast with that in VWF suggesting that endothelin-1 is related to sympathetic hyperactivity which is more involved in PRP rather than VWF. It seems unlikely that endothelin-1 is functionally or directly associated with CIVD.

Adult↗

Renal reabsorption of magnesium and calcium by cattle with renal tubular dysplasia.

The concentrations of magnesium and calcium in the serum and urine and their rates of clearance were determined in cattle with renal tubular dysplasia, an autosomal recessive hereditary disease associated with a deletion of the paracellin-1 gene in Japanese Black cattle. There were no significant differences in the serum or urine magnesium concentrations between normal cattle and cattle which were heterozygous or homozygous for the condition. Serum calcium concentrations tended to be lower in the homozygous cattle, and the serum creatinine and urea nitrogen concentrations were significantly higher in the homozygous cattle. The ratio of magnesium:creatinine and the fractional excretion of magnesium were higher in cattle with the disease than in normal cattle. There were no significant differences in urine calcium concentration, the calcium:creatinine ratio, and fractional excretion of calcium between normal cattle and cattle which were homozygous or heterozygous for the condition. The creatinine clearance was significantly lower in the homozygous cattle than in normal cattle. The clearance, excretion rate, reabsorption rate and reabsorption rate:clearance ratio of magnesium in cattle with renal tubular dysplasia were significantly lower than in normal cattle. The clearance rate and reabsorption rate of calcium were also significantly lower in the affected cattle, but the excretion rate and reabsorption rate:clearance of calcium were not different between the normal cattle and the cattle homozygous for the condition. In cattle with the condition the rate of reabsorption of magnesium by the kidneys was low, but the rate of reabsorption of calcium was normal.

Absorption↗

Immune evasion strategies of Kaposi's sarcoma-associated herpesvirus.

To establish lifelong infection in the presence of an active host immune system, herpesviruses have acquired an impressive array of immune modulatory mechanisms that contribute to their success as long-term parasites. Kaposi's sarcoma-associated herpesvirus (KSHV) is the most recently discovered human tumor virus and is associated with the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. KSHV has acquired a battery of genes to assist in viral survival against the host immune response. These viral gene products target a variety of host immune surveillance mechanisms, including the cytokine-mediated immune response, apoptosis, natural killer (NK) cell killing and T cell-mediated responses. This review summarizes our understanding of the role of these viral proteins in the escape from host immune surveillance, which ultimately contributes to lifelong infection and pathogenesis of KSHV.

Animals↗

A study on the estimation of sulfur-containing amino acid metabolism by the determination of urinary sulfate and taurine.

Sulfate and taurine are major end products of sulfur-containing amino acid metabolism in mammals including humans, and they are excreted in urine. Average excretions micromol/mg of creatinine) in the morning urine of 58 female college students were: total (free plus ester) sulfate (a). 12.53 +/- 3.85; free sulfate, 11.57 +/- 3.69; taurine, 0.78 +/- 0.53. Ratio of total sulfate and taurine was 10 : 0.6. Regression lines obtained by plotting total sulfate, free sulfate, or total sulfate plus taurine against urea have shown that the former excretions are significantly correlated with urea excretion. Excretion of total sulfate at zero point of urea excretion (b). was 5.30, which corresponded to 42.3% of average excretion (12.53) and was assumed to be derived from dietary sulfate. The difference 7.23 (a - b) seemed to be derived from sulfur-containing amino acids. It was pointed out that the difference of average sulfate excretion and sulfate excretion at zero urea excretion, namely a - b, was appropriate for the metabolic index of sulfur-containing amino acids of the group examined. As free sulfate constituted 92.3% of total sulfate, excretion of ester sulfate was at a constant level, and that of taurine was not significantly correlated with urea excretion, the value of free sulfate corresponding to the value a - b of total sulfate mentioned above seemed to be a reliable and convenient index in the assessment of sulfur-containing amino acid metabolism.

Adolescent↗

Ectopic bone formation by electroporatic transfer of bone morphogenetic protein-4 gene.

Orthopedic surgeons have long awaited the clinical application of bone morphogenetic proteins (BMPs) for bone regeneration. However, such possible applications involving proteins or genes transferred with virus vectors have encountered many problems, including high cost, immunological reactions, viral infection, etc. We adopted a new gene transfer system of in vivo electroporation with a plasmid expression vector. A solution of plasmid DNA containing mouse BMP-4 (pMiw-BMP4) was injected into the gastrocnemius of BALB/cA mice, and electric pulses were applied through paired-needle electrodes inserted percutaneously. As a control plasmid, LacZ-containing plasmid (pMiwZ) was transferred by electroporation. A control group in which pMiw-BMP4 was injected and not electroporated was also introduced. In these groups, the gastrocnemius was harvested at 7, 14, 21, and 28 days after electroporation (n = 6 in each). As nonplasmid controls, electroporation with saline injection (n = 6), electroporation without injection (n = 6), and saline injection only (n = 3) were prepared. In these groups, the mice were killed 7 days after experimentation. Ectopic calcification or ossification was examined by histology as well as soft X-ray. In all electroporated groups (pMiwZ, pMiw-BMP4, saline injection, and without injection), dystrophic calcification of muscle bundles and infiltration of mesenchymal cells were observed histologically. Ectopic bone formation was observed only in the pMiw-BMP4 electroporation group. At 7 days after pMiw-BMP4 electroporation, extracellular eosinophilic matrix in a collection of mesenchymal cells was observed. Between 14 and 28 days after electroporation, ectopic bone was observed in 44% of mice, and bone marrow-like cells observed in 22%. The newly formed bone was woven. Injection of pMiw-BMP4 or saline induced neither calcification nor ossification. Our findings indicate that BMP-4 transferred by electroporation can induce in vivo and in situ ectopic bone formation in skeletal muscle.

Animals↗

An outbreak of gastroenteritis in Osaka, Japan due to Escherichia coli serogroup O166:H15 that had a coding gene for enteroaggregative E. coli heat-stable enterotoxin 1 (EAST1).

In an outbreak of gastroenteritis on 23 July 1996, in Osaka, Japan, 54 of 91 persons who had attended a meeting the previous day became ill. Escherichia coli O166:H15 was isolated from stool specimens of patients (29/33, 88%). Laboratory tests for other bacterial pathogens and viruses were negative. The E. coli 0166 organisms did not adhere to HEp-2 cells in a localized, diffuse, or enteroaggregative manner. The organisms did not express known enterotoxigenic E. coli (ETEC) colonization factors. In polymerase chain reaction tests, the bacteria did not have coding genes for shigatoxin of enterohemorrhagic E. coli (EHEC), heat-labile, or heat-stable enterotoxin of ETEC, attachment and effacement (eaeA) of EPEC, or invasion (invE) of enteroinvasive E. coli (EIEC). Consequently, they could not be assigned to any of the recognized diarrhoeagenic groups of E. coli: EPEC, ETEC, EHEC, EIEC, enteroaggregative E. coli (EAggEC), or diffusely adhering E. coli. However, the organisms possessed the EAggEC heat-stable enterotoxin (EAST1) gene. To our knowledge, this is the first report of an outbreak caused by E. coli that did not have well-characterized virulence genes other than EAST1. The isolates showed the same DNA banding pattern in pulsed-field gel electrophoresis after digestion with the restriction enzymes XbaI or NotI. Three O166:H15 strains isolated from two sporadic cases and another outbreak during 1997-8 were distinct, indicating that multiple clones have spread already. We propose that diarrhoeal specimens should be examined for E. coli possessing the EAST1 gene.

Base Sequence↗

Introduction of DNA enzyme for Egr-1 into tubulointerstitial fibroblasts by electroporation reduced interstitial alpha-smooth muscle actin expression and fibrosis in unilateral ureteral obstruction (UUO) rats.

The phenotypic alteration of interstitial fibroblasts into 'myofibroblasts', acquiring characteristics of both fibroblasts and smooth muscle cells is a key event in the formation of tubulointerstitial fibrosis. The up-regulation of the early growth response gene 1 (Egr-1) preceded the increased interstitial expression of alpha-smooth muscle actin (alphaSMA), a marker of phenotypic changes, in obstructed kidney, a model of interstitial fibrosis. To target Egr-1 expression in the interstitium of obstructed kidneys, we introduced a DNA enzyme for Egr-1 (ED5) or scrambled DNA (SCR) into interstitial fibroblasts by electroporation-mediated gene transfer. Northern blot analysis confirmed an increase in the cortical mRNA expression of Egr-1 in the obstructed kidneys from untreated or SCR-treated rats, while ED5 transfection blocked Egr-1 expression with a concomitant reduction in TGF-beta, alphaSMA and type I collagen mRNA expression. Consequently, ED5 inhibited interstitial fibrosis. In conclusion, electroporation-mediated retrograde gene transfer can be an ideal vehicle into interstitial fibroblasts, and molecular intervention of Egr-1 in the interstitium may become a new therapeutic strategy for interstitial fibrosis.

Actins↗

Prevention and regression of atopic dermatitis by ointment containing NF-kB decoy oligodeoxynucleotides in NC/Nga atopic mouse model.

Atopic dermatitis, a chronic inflammatory skin disease characterized by relapsing eczema and intense prurigo, requires effective and safe pharmacological therapy. In this study, we examined the efficacy of ointment containing NF-kB decoy oligodeoxynucleotides (ODN) on atopic dermatitis lesions in NC/Nga mice, which are characterized by the spontaneous onset of atopic dermatitis in conventional conditions. Topical administration of NF-kB decoy ODN twice a month resulted in a significant reduction in clinical skin condition score and marked improvement of histological findings. Reduction of the atopic skin condition by NF-kB decoy ODN was accompanied by a significant decrease in migration of mast cells into the dermis and an increase in apoptotic cells. Here, we demonstrated the successful treatment of atopic dermatitis with ointment containing NF-kB decoy ODN in a mouse model, promising new therapy for atopic dermatitis.

Administration, Cutaneous↗

Bacteroides forsythus hemagglutinin is inhibited by N-acetylneuraminyllactose.

Bacteroides forsythus, which has been recognized as a pathogen associated with periodontitis, produces a hemagglutinin. The hemagglutinin was localized in the envelope of B. forsythus. The hemagglutinating activity was inhibited by lactose at concentrations as low as 1 mM, and by L-arginine and L-lysine at concentrations of 100 mM. N-Acetylneuraminyllactose (NeuAc-lactose) was at least 100 times more potent an inhibitor than lactose, as it completely inhibited the hemagglutination at concentrations below 10 microM. This is similar to the Helicobacter pylori hemagglutinin. The hemagglutinin was heat-labile, and resistant to treatment with proteases such as trypsin. A specific antibody raised against one of the S-layer proteins that are major species-specific proteins had no inhibitory effect on the hemmaglutination. These results suggest that the NeuAc-lactose-sensitive adhesin of B. forsythus may play an important role in colonization in the oral cavity.

Adhesins, Bacterial↗

Serum pepsinogen can predict response to H2-receptor antagonist in patients with functional dyspepsia.

BACKGROUND: Therapy for the relief of symptoms of functional dyspepsia is unpredictable. AIM: To identify which patients may benefit from antisecretory therapy. METHODS: Twenty-seven patients with functional dyspepsia were selected to receive H2-receptor antagonist (H2RA) treatment for 4 weeks. Serum pepsinogen A, pepsinogen C and gastrin were measured, and Helicobacter pylori status was determined. Symptoms were assessed at baseline and after H2RA treatment. RESULTS: Fourteen patients were identified as H2RA responders and the remaining patients were non-responders. No differences were found between responders and non-responders with regard to serum pepsinogen A, pepsinogen C, gastrin and H. pylori status. However, the pepsinogen A/C ratio was significantly higher in responders than in non-responders. Ten of the 13 functional dyspepsia patients (77%) with a high value of the pepsinogen A/C ratio (> or = 4.5) achieved symptom resolution by H2RA, compared with only one of the eight patients (13%) with a low value of the pepsinogen A/C ratio (< or = 3.0). CONCLUSIONS: The serum pepsinogen A/C ratio seems to identify those functional dyspepsia patients for whom acid control provides benefit. This ratio may be a practical tool for the management of functional dyspepsia patients.

Adult↗

A novel A97P amino acid substitution in alpha-galactosidase A leads to a classical Fabry disease with cardiac manifestations.

BACKGROUND: Fabry disease results from a genetic deficiency of alpha-galactosidase A (GLA) activity. Phenotype-genotype correlations in this condition have not as yet been fully elucidated. OBJECTIVE: To report a case of a male patient with classical Fabry disease and his mother, a heterozygous female with Fabry disease, showing cardiac involvement, and to identify the underlying GLA gene mutation in this particular phenotype. PATIENTS/METHODS: Genomic DNA was extracted from the patient, his mother and the unaffected family members. Biopsy specimens of skin, heart and kidney were examined using light and electron microscopy. The mutation was identified by polymerase chain reaction and direct sequencing and was confirmed by restriction enzyme fragment length polymorphism. RESULTS: The G-->C transversion was identified in codon 97 of the GLA gene and resulted in an A97P amino acid substitution that was a novel pathogenic GLA gene mutation. The male patient who had classical Fabry disease was hemizygous and his mother was heterozygous for this mutation. CONCLUSIONS: These results indicate that the A97P amino acid substitution in GLA might tend to induce classical Fabry disease.

Adult↗

Conserved CDR 3 region of T cell receptor BV gene in lymphocytes from bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an inflammatory lung disease characterized by the accumulation of inflammatory cells and deposition of collagen, resulting in lung remodelling. High numbers of T cells are present in bronchoalveolar lavage fluid (BALF) of IPF patients, although the characteristics of these cells are yet to be determined. To elucidate the pathogenic mechanisms of IPF, we analysed the T cell receptor (TCR) of BALF lymphocytes in three patients with IPF and three healthy subjects as control. TCR repertoire of BALF lymphocytes and T cell clonality were examined by family PCR and Southern blot analysis, and single-strand conformation polymorphism (SSCP), respectively. We observed that the TCR repertoire in the lung was heterogeneous, both in the control subjects and three patients with IPF. SSCP analysis demonstrated an increase in the number of accumulated T cell clones in BALF of two of the three patients, but not in the healthy subject. Furthermore, junctional sequence analysis showed the presence of conserved amino acid motifs (ETGRSG, LAxG, QGQ, GxQP, GRxG, VAR, PGT, GTI, GGT, TGR, LxLxQ, SGQ) in the TCR-CDR 3 region of BAL lymphocytes in patients with IPF, whereas only two amino acid motifs (VTTG, GGE) were found in the control. Our findings suggest that T cells in BALF of patients with IPF expand oligoclonally in the lung, suggesting antigen stimulation of these cells.

Adult↗