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Biomedical subjects

H Nakamura

Publications and source records attributed to H Nakamura.

At least 91 records · Page 5Linked to original sources
PubMed2003

A functional MRI study of somatotopic representation of somatosensory stimulation in the cerebellum.

Somatotopic representation in the cerebral cortex of somatosensory stimulation has been widely reported, but that in the cerebellum has not. We investigated the latter in the human cerebellum by functional MRI (fMRI). Using a 1.5 tesla imager, we obtained multislice blood oxygen level-dependent fMRI with single-shot gradient-echo echoplanar imaging in seven right-handed volunteers during electrical stimulation of the left index finger and big toe. In the anterior and posterior cerebellum, activated pixels for the index finger were separate from those for the toe. This suggests that somatosensory stimulation of different parts of the body may involve distinct areas of in the cerebellum as well as the cerebral cortex.

Adult↗
PubMed2003

Effects of edaravone on experimental brain injury in view of free radical reaction.

The purpose of this study is to clarify the influence of a novel free radical scavenger edaravone on experimental brain injury. Male Wistar rats were anesthetized with 1-2% halothane. Brain injury was produced using a controlled cortical impact injury device. Experimental rats were divided into 2 groups. In the edaravone group, edaravone (3 mg/kg) was twice administered intravenously for 30 minutes. In the saline group, saline solution was administered in the same way. This administration of edaravone or saline solution made it possible to evaluate the relative effects of edaravone by assessment of free radical reaction and water content. As a result, the level of oxygen free radicals at 50 minutes after brain injury was significantly lower in the edaravone group than in the saline group. The water content in the injured brain at 180 minutes was significantly lower in the edaravone group than in the saline group. Therefore, we propose that edaravone may be effective for treatment in head injury.

Animals↗
PubMed2003

Analysis of dystrophin mRNA from skeletal muscle but not from lymphocytes led to identification of a novel nonsense mutation in a carrier of Duchenne muscular dystrophy.

Dystrophin mRNA expressed in peripheral lymphocytes of individuals with X-linked Duchenne muscular dystrophy (DMD) has been used as a source material for mutation analysis. Here we present the first report of failure of isolation of nonsense dystrophin mRNA in lymphocytes but success in skeletal muscle in a female carrier of DMD. The mutation responsible for dystrophin-negative muscle fibers of the carrier was analysed by direct sequencing of the reverse transcription PCR product of dystrophin mRNA. In her peripheral lymphocytes, no nucleotide change was detected in the 14 kb long mRNA. Remarkably, a novel nucleotide change of C1682T in exon 12, changing glutamine codon to stop codon (Q492X) was found to be present in her skeletal muscle. This change was heterozygous. Analysis of her genomic DNA disclosed heterozygous C and T nucleotides at nt 1682, confirming the genomic origin of the nonsense mutation. Although dystrophin cDNA prepared from lymphocytes was sequenced again after subcloning, mutation-retaining clone could not be isolated. This lymphocyte-specific disappearance of nonsense mRNA strongly suggested tissue-specific skewing of X-inactivation. However, both paternal and maternal dystrophin alleles were shown to be equally expressed in lymphocytes as well as in muscle, indicating no skewing of X-inactivation in lymphocytes. We concluded that the dystrophin mRNA of the DMD carrier was destabilized in lymphocytes. Our results indicated that analysis of mRNA in lymphocytes is not enough for exact carrier diagnosis of Duchenne muscular dystrophy.

Adult↗
PubMed2003

Effects of thioredoxin on the preimplantation development of bovine embryos.

Thioredoxin (TRX) is an ubiquitous protein disulfide reductase, which is known to be involved in the implantation development of mouse embryos. In the present study, recombinant human TRX was used to evaluate its effect on the promotion of preimplantation development of bovine embryos derived from in vitro maturation and fertilization. Supplementation of the medium 24h post insemination with TRX significantly (P<0.05) enhanced the frequency of development to the blastocyst stage in 5% O(2) concentration. The optimal concentration was 0.5 microg/ml (P<0.05, compared with 0, 0.1 and 1.0 microg/ml). This effect of TRX was evident only when added around the time of the first cleavage stage (24 h post insemination); no promotion was found with treatment at 6h (one-cell) or 44 h (six- to eight-cell) after insemination. Moreover, it is of interest that even with the best combination of the dose and timing of TRX treatment (0.5 microg/ml, at 24 h post insemination), no promotion of development was observed when embryos were cultured under 20% O(2). However, a preincubation of TRX in the culture medium under 20% oxygen for 24h did not diminish the promoting effect in the subsequent TRX treatment under optimal conditions, thus suggesting that the possible oxidation of TRX alone may not be the reason for the disappearance of the effect under a high oxygen concentration. These results indicate that TRX does improve the development of bovine embryos in vitro, though unlike the general reducing reagents such as beta-mercaptoethanol or cysteamine, TRX may have to exert its effect at specific times and in more physiologic oxygen environments.

Animals↗
PubMed2003

Effects of an aldose reductase inhibitor on gastroenteropathy in streptozotocin-diabetic rats.

We investigated the effects of epalrestat, an aldose reductase inhibitor (ARI), on gastric emptying, fecal water content, and electrolyte transport in distal colon in streptozotocin (STZ)-induced diabetic rats. We measured gastric emptying time by acetaminophen method and short-circuit-current (Isc) in colonic mucosa using an Ussing chamber. The Isc in response to electric-field-stimulation (EFS) was decreased in untreated rats due to suppression by Cl- secretion. ARI treatment alleviated this suppression (2.7 +/- 0.6 vs. 7.4 +/- 1.1 microA/0.38 cm2 at 8 weeks after treatment, 1.1 +/- 0.2 vs. 7.0 +/- 1.0 at 12 weeks after treatment, P<0.05). In addition, the percentage of fecal water content in untreated rats was significantly lower than in ARI-treated rats (58.0 +/- 2.0 vs. 67.6 +/- 0.8% at 8 weeks, 56.9 +/- 2.1 vs. 63.4 +/- 1.4 at 12 weeks, P<0.05). From STZ injection to 8 weeks, the serum levels of acetaminophen in the diabetic rats were significantly lower than in controls, indicating delayed gastric emptying. At 12 weeks in the diabetic rats treated with ARI, the serum levels of acetaminophen were significantly higher than in the untreated diabetic rats (6.6 +/- 0.4 vs. 3.5 +/- 0.5 microg/ml, P<0.05). ARI-treatment ameliorated delayed gastric emptying without improving glycemic control. These findings show that ARI partially prevented progression of impaired gastric emptying, ion transport, and water transport, and suggest that epalrestat might be useful in the treatment of diabetic gastroenteropathy.

Acetaminophen↗
PubMed2003

A subchronic toxicity study of shea nut color in Wistar rats.

Shea nut color, obtained from nuts of the shea tree (Butyrospermum parkii), is used as a food-coloring agent. Flavonoid pigments are considered to be the responsible constituents. As there have been no reports of toxicological evaluation, a 13-week subchronic toxicity study was performed in Wistar Hannover rats at dose levels of 0 (control), 0.07, 0.31, 1.25 and 5% in powdered basal diet. The average of daily shea nut color intake was 51.3, 226.1, 986.8 and 3775.5 mg/kg/day for males and 56.4, 272.9, 1166.7 and 4387.7 mg/kg/day for females, respectively. During the administration period, daily observation of clinical signs and weekly measurement of body weights and food consumption were performed. After the end of the treatment, hematology, serum biochemistry, organ weight and histopathological examinations were conducted. No significant toxicological changes were observed in any parameters in this study. Hence, the no adverse effect dose of shea nut color was estimated to be greater than 5.0% for both sexes (3775.5 mg/kg/day for males and 4387.7 mg/kg/day for females).

Animals↗
PubMed2003

Squamous cell carcinoma developing in a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa.

We report a 12-year-old boy with nonHallopeau-Siemens recessive dystrophic epidermolysis bullosa (nHS-RDEB) who developed two skin lesions of squamous cell carcinoma (SCC) on the left foot. The incidence of SCC in nHS-RDEB is much lower than in the HS-RDEB subtype. Furthermore, this boy is the youngest among 92 previously described patients with DEB to develop SCC. This study emphasizes the importance of vigilance in monitoring the possible development of SCC in DEB patients regardless of age or clinical severity.

Age of Onset↗
PubMed2003

Subcutaneous nodules on the buttocks as a manifestation of dialysis-related amyloidosis: a clinicopathological entity?

While beta 2-microglobulin amyloidosis occurring in patients undergoing long-term dialysis is frequently associated with joint involvement, skin lesions have rarely been encountered. We report a 57-year-old man with extensive subcutaneous amyloid deposition forming large nodules on the buttocks; the patient had been on maintenance dialysis for 28 years. Although this condition is rare, a review of the literature indicates that the majority of such lesions occur around the buttock region.

Amyloidosis↗
PubMed2003

Th1/Th2 profile in peripheral blood in atopic cough and atopic asthma.

BACKGROUND: Eosinophilic tracheobronchitis with cough hypersensitivity, abbreviated as atopic cough, is an important cause of chronic cough. The reason for the absence of airway hyper-responsiveness is unknown, differing from asthma, a Th2 cytokine-mediated disorder. OBJECTIVE: To compare the type 1 helper T cell (Th1)/Th2 balance in the peripheral blood from subjects with atopic cough and atopic asthma, we assessed the intracellular cytokine production at the single-cell level. METHODS: Thirty-six subjects (10 patients with atopic cough, 18 with atopic asthma, and eight control subjects) were included. Intracellular IL-4 and IFN-gamma were detected in CD4+ T cells by flow cytometry. RESULTS: A significantly lower ratio of IFN-gamma-/IL-4-producing CD4+ T cells after phorbol 12-myristate acetate/ionomycin stimulation was found in patients with atopic cough and atopic asthma compared with normal subjects. In comparison between atopic patients, the ratio of IFN-gamma-/IL-4-producing cells was significantly higher in atopic cough than in atopic asthma. However, the proportion of IL-4-producing CD4+ T cells was significantly higher in patients with atopic asthma than in normal control subjects and no significant difference was detected between patients with atopic cough and normal subjects. No significant difference in the proportion of IFN-gamma-producing cells was found between the subjects. Overall, the total IgE levels were positively correlated to the IL-4-producing cells and inversely correlated to the ratio of IFN-gamma-/IL-4-producing cells. CONCLUSION: These results show the lower degree of Th2 cytokine predominance in atopic cough compared with atopic asthma and suggest the relation between the Th1/Th2 balance and atopic status.

Adult↗
PubMed2003

Green tea-induced asthma: relationship between immunological reactivity, specific and non-specific bronchial responsiveness.

BACKGROUND: The relationships between immunological reactivity and bronchial responsiveness to allergen and non-specific bronchial responsiveness are unclear in occupational asthma caused by low molecular weight substances. OBJECTIVE: We assessed the above relationships in green tea-induced asthma, an occupational asthma of green tea factory workers, in which epigallocatechin gallate (EGCg), a low molecular weight component of green tea leaves, is the causative agent. METHODS: Subjects consisted of 21 patients suspected of having green tea-induced asthma, on whom skin test and inhalation challenge with EGCg were performed. The skin sensitivity or end-point titration to EGCg as a measure of immunological reactivity, together with the provocative concentrations causing a 20% or greater fall in forced expiratory volume in 1 s (PC20) of EGCg and methacholine, were determined. RESULTS: We found that 11 patients had green tea-induced asthma, with immediate asthmatic reactions in eight and dual asthmatic reactions in three. We also found that 11 of 13 patients (85%) with immunological reactivity and bronchial hyper-responsiveness to methacholine experienced an asthmatic reaction and that no subject without immunological reactivity reacted. There were significant correlations among skin sensitivity, EGCg PC20 and methacholine PC20. Multiple linear regression analysis showed the relationship: log (EGCg PC20)=0.42 log (skin sensitivity)+1.17 log (methacholine PC20)+0.93 (r=0.796, P<0.05). CONCLUSION: It is concluded that bronchial responsiveness to EGCg can be highly satisfactorily predicted by skin sensitivity to EGCg and bronchial responsiveness to methacholine.

Adult↗
PubMed2003

Role of interleukin-12 in the regulation of CD4+ T cell apoptosis in a mouse model of asthma.

Allergic asthma, a chronic inflammatory disease of the airways, is characterized by the presence of T helper 2 cells and eosinophils in sputum, bronchoalveolar lavage, and mucosal biopsy specimens. Although the T helper 1-promoting cytokine, interleukin-12, is capable of inhibiting the T helper 2-driven asthma symptoms and bronchial responsiveness, the specific mechanisms underlying these interleukin-12 actions are unclear. The anti-allergic response to interleukin-12 is only partially dependent on interferon-gamma, which induces apoptosis by enhancing expression of Fas antigen. We therefore investigated in vivo whether the anti-allergic action of interleukin-12 is mediated through induction of apoptosis. C57BL/6 mice immunized to ovalbumin by intraperitoneal injection were challenged three times with an ovalbumin aerosol every second day for 7 days. Recombinant interleukin-12 was administered intravenously after the final challenge. After the last ovalbumin challenge, mice were examined for effects of interleukin-12 on inflammatory cell infiltration and apoptosis in the lung as detected by terminal deoxynucleotidyl transferase-mediated deoxyribonucleoside triphosphate nick end-labelling. Administration of interleukin-12 reduced ovalbumin-induced pulmonary eosinophilia (P < 0.01) and CD4+ T cell infiltration (P < 0.01). Moreover, treatment with interleukin-12 shortly after ovalbumin inhalation resulted in both increased interferon-gamma production (P < 0.01) and enhanced apoptosis of CD4+ T cells in allergic airway infiltrates (P < 0.05). These results suggest that the beneficial effects of interleukin-12 in asthma may include enhancement of apoptosis of CD4+ T cells in airways.

Animals↗
PubMed2003

Presence of pannus-like tissue on osteoarthritic cartilage and its histological character.

OBJECTIVE: To investigate and characterize pannus-like tissue which is often present on osteoarthritic articular cartilage. DESIGN: Cartilage specimens from 15 knee and five hip joints of patients with osteoarthritis (OA) undergoing arthroplasty were stained for HE and Safranin-O. They were also immunostained by antitype I collagen, type II collagen, CD68, IL-1beta and MMP3 antibodies. RESULTS: Ninety percent of joints have pannus-like tissue on the articular surface, preferentially in a marginal area. The articular cartilage was divided into three regions according to the location: the marginal zone, the intermediate zone and the paraeburnated zone. Pannuslike tissue in OA knee joint occurred 45.9%, 27.5% and 11.1% of the surface of each region respectively. Histologically, pannus-like tissue could be classified into the vascular type and the fibrous type. Extracellular matrix of both types of tissues were negative for Safranin-O and type II collagen, but positive for type I collagen. IL-1beta and MMP3 expressing cells are predominant in pannus-like tissue, whereas CD68 positive cells were infiltrated in only a few samples. Vascular type tissue kept continuity with bone marrow suggesting mesenchymal origin. CONCLUSION: Pannus-like tissue exists in advanced OA cartilage, preferentially in the marginal zone. It expressed IL-1beta and MMP3, which strongly suggests that it contributes to cartilage degradation.

Aged↗
PubMed2003

Expression and activity of matrix metalloproteinase 2 and 9 in human trophoblasts.

Indiscriminate invasion upon the endometrium by normal trophoblasts is strictly regulated unlike that by choriocarcinoma cells. In this study, we focused on the activity of matrix metalloproteinase (MMP)-2 and MMP-9 as parameters of invasion in normal human placenta. In situ hybridization (ISH), immunohistochemical staining (IH) and film in situ zymography (FIZ) were performed to identify cells having MMP-2 or MMP-9 expression and activity. Purified cytotrophoblasts (CTs) were used to examine the expression and activity of MMP-2 and MMP-9, and their invasive ability. In first trimester placental tissue, the MMP-2 expression was observed in extravillous trophoblasts (EVTs), and MMP-9 mainly in villous cytotrophoblasts (VCTs). FIZ revealed marked gelatinase activity in the EVTs which MMP-2 expression was observed in. In full-term placental tissue, the MMP-2 expressions was observed in the EVTs similar to that in first trimester, whereas the gelatinase activity in these cells was decreased or completely lost. Using purified CTs, the gelatinase activity was marked in early CTs, but not term CTs. Invasive ability of early CTs was inhibited by tissue inhibitor of metalloproteinase (TIMP)-2 and MMP-2 antibody in a dose dependent manner. These suggests that the invasive ability of trophoblasts may be regulated by the enzyme activity of gelatinases, especially MMP-2.

Adult↗
PubMed2003

A morphological and immunolabeling study of freeze-substituted Bacteroides forsythus.

We used a rapid freezing and freeze-substitution technique without glutaraldehyde and OsO4 fixation for the electron microscopic immunocytochemical demonstration of the surface structure of Bacteroides forsythus, an anaerobic Gram-negative periodontopathogen. Cells were applied to pieces of filter paper and freeze-substituted by plunge-freezing in liquid propane, substituted in methanol containing 0.5% uranyl acetate, and infiltrated with LR White resin. The membrane ultrastructure of B. forsythus was preserved well, and the labeling density of the freeze-submitted cells was compared to a conventional processing method. Our results show the usefulness of the freeze-substitution method for immunohistochemical studies of B. forsythus.

Bacteroides↗
PubMed2003

Risk factors for age related maculopathy in a Japanese population: the Hisayama study.

AIMS: To examine the risk factors for age related maculopathy (ARM) in a sample Japanese population. METHODS: In 1998, a cross sectional community survey was conducted among residents of Hisayama. A total of 596 men and 886 women living in Hisayama, Japan, aged 50 years or older consented to participate in the study. Each participant underwent a comprehensive examination that included an ophthalmic examination. The presence of ARM was determined by grading from fundus examination by indirect ophthalmoscopy, slit lamp examination, and colour fundus photographs. Using these cross sectional data, logistic regression analyses were performed to determine the risk factors for ARM. The following 10 possible risk factors were used: age, cataract, hypertension (history), hypertension (history or examination), diabetes, hyperlipidaemia, current smoker, alcohol intake, BMI, and WBC. RESULTS: ARM was detected in 19.5% of men and 14.9% of women. Men were found to have a significantly higher prevalence of ARM than women. Multiple logistic regression analysis showed that age and hypertension (history or examination) were significantly associated with ARM in men, whereas only age was a significant risk factor for ARM in women. CONCLUSIONS: This study suggests that higher age and male sex are relevant risk factors for ARM in Japan. In addition, hypertension is a relevant risk factor in men.

Age Distribution↗
PubMed2003

Association of CYP2A6 deletion polymorphism with smoking habit and development of pulmonary emphysema.

BACKGROUND: Nicotine is responsible for smoking dependence and is mainly metabolised by CYP2A6. Several types of genetic polymorphism of CYP2A6 have been reported, but their relation to smoking habit and chronic obstructive pulmonary disease (COPD) phenotypes has not been fully clarified. METHODS: 203 current or ex-smokers (lifelong cigarette consumption (CC) >/=10 pack years) with subclinical and established COPD phenotypes were clinically evaluated and pulmonary function tests and a chest CT scan were performed (smoker group). The non-smoker group consisted of 123 healthy volunteers. CYP2A6 genotypes were determined in both groups. RESULTS: The percentage of subjects with a CYP2A6del allele (genotype D) was lower in heavy smokers (20.5%, n=88, CC >/=60 pack years) than in light smokers (37.4%, n=115, CC 10-59 pack years, chi(2)=6.8, p=0.01) or non-smokers (36.1%, n=122, chi(2)=6.0, p=0.01); lower in ex-smokers (20.7%, n=111) than in current smokers (41.3%, n=92, chi(2)=10.1, p<0.01); and lower in smokers with a high LAA (low attenuation area) score on the chest CT scan (18.4%, n=76, LAA >/=8.0) than in those with a low LAA score (37.0%, n=127, LAA <8.0, chi(2)=7.8, p<0.01). CONCLUSIONS: Subjects with the CYP2A6del allele tend not to be heavy habitual smokers but can be light habitual smokers. The CYP2A6del polymorphism may inhibit smokers from giving up smoking, but appears to function as a protective factor against the development of pulmonary emphysema independent of smoking habit.

Aged↗