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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 37 records · Page 2Linked to original sources

Present characteristics of symptomatic Entamoeba histolytica infection in the big cities of Japan.

Medical records, for 2000 and 2001, of symptomatic amoebic patients who were treated at our hospitals in Tokyo, Yokohama and Osaka were studied retrospectively for the purpose of gathering epidemiological data on symptomatic Entamoeba histolytica infection. A total of 58 patients were treated. Fifty-five of them were male, and 96% of the male patients were Japanese. The mean age of patients was 44.9 years old, and 91% of patients contracted the disease in Japan. Fifty-six per cent of the male patients indicated that they were practising homosexuals, and 44% of the male patients denied these practices or left the question unanswered. The serum Treponema pallidum haemagglutination test was positive in 45% of the patients, and antibody to human immunodeficiency virus (HIV) was positive in 45%. Our study revealed that recent symptomatic E. histolytica infection almost exclusively afflicted middle-aged males in the big cities of Japan, that a majority of the patients were probably exposed to the causative organism during homosexual activity, and that an increasing number of patients will be co-infected with HIV.

AIDS Serodiagnosis↗

Excess accumulation of body fat is related to dyslipidemia in normal-weight subjects.

OBJECTIVE: To assess the relationship of fat mass (FM) and its distribution to hypertension and dyslipidemia in normal-weight Japanese individuals. DESIGN: Cross-sectional study. SUBJECTS: Apparently healthy Japanese subjects with a body mass index (BMI) between 20 and 23.5 kg/m(2) (265 males and 741 females, age 21-69 y). MEASUREMENTS: BMI, waist circumference (WC), waist-hip ratio (WHR), systolic and diastolic blood pressure, serum levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) were measured. Low-density lipoprotein-cholesterol (LDL-C) was calculated by the Friedewald formula. Percentage fat mass (%FM) and trunk fat mass-leg fat mass ratio (FM(trunk)/FM(legs)) were obtained by dual-energy X-ray absorptiometry. RESULTS: WC, WHR, %FM and FM(trunk)/FM(legs) were significantly correlated with TC, LDL-C, HDL-C and TG with the tendency of FM(trunk)/FM(legs) to show the strongest correlations. For %FM and FM(trunk)/FM(legs) in both sexes, odds ratios (ORs) of the third tertiles with respect to the first tertiles increased for LDL-C elevation, TG elevation and dyslipidemia. In males, ORs of the third tertiles of WC were significantly high for LDL-C elevation and dyslipidemia whereas those of WHR were high for TG elevation and dyslipidemia. ORs of the third tertiles of WC and WHR were significantly high for TG elevation in females. BMI was not associated with the risk of abnormal lipid levels. ORs for hypertension showed significant increases in none of the variables of obesity. CONCLUSIONS: Excess accumulation of FM, especially to the upper body, was related to dyslipidemia in normal-weight subjects. Simple anthropometric variables, WC and WHR, may be useful for screening and management of dyslipidemia in these subjects.

Absorptiometry, Photon↗

Insulin-like growth factor-I stimulates acromegaly-like specific mandibular enlargement in rats.

To help us investigate the time course of mandibular enlargement in acromegaly or acrogiantism to determine the most suitable period for occlusal treatment in this disease, our aim was to develop a rat model of acromegaly (acrogiantism). In this study, prominent mandibular enlargement was induced by continuous subcutaneous infusion of human recombinant insulin-like growth factor-I (IGF-I) (640 microg/day) in 10-week-old male rats for 4 weeks (n = 6); the control sham-operated group was injected with saline alone (n = 6). Circulating human IGF-I was clearly detectable in the IGF-I group during the four-week administration period, while endogenous rat IGF-I levels decreased. Total IGF-I (human + rat) increased significantly during administration, returning to control levels afterwards. The length of every bone examined (mandible, maxilla, and femur) showed a significant increase compared to control rats, especially the mandible. Although the mandible did not continue to grow after discontinuation of IGF-I administration, it did not return to control size, unlike the maxilla and femur, and disharmonious jaw size (between maxilla and mandible) persisted even after circulating IGF-I levels normalized. These findings in our rat model suggest that mandibular occlusal treatment should only be considered for acromegalic (acrogiantic) patients after serum IGF-I levels have normalized and bone growth has ceased.

Acromegaly↗

Use of diffusion-weighted magnetic resonance imaging in empyema after cranioplasty.

External decompression can be an effective treatment for acute intracranial hypertension, but the cranial defect must be repaired. The most serious complication of cranioplasty is late infection. Confusing an empyema that occurs after cranioplasty with a fluid collection (haematoma or liquor) can have catastrophic consequences, such as the development of cerebritis. The goal of this study was to assess the ability of diffusion-weighted (DW) magnetic resonance imaging (MRI) to diagnose empyema after cranioplasty. DW MRI and apparent diffusion coefficient (ADC) maps were studied in six patients with surgically verified empyema after cranioplasty. The findings were compared with those in five patients who had surgically verified haematoma or liquorrhoea. In the patients with empyema, the lesion was hyperintense, whereas the fluid collections (haematoma and liquorrhoea) were visualized as hypointense lesions. The ADC maps showed that empyema had a significantly lower intensity than the fluid collections (haematoma or liquorrhoea). DW MRI can be used to identify empyema after cranioplasty and can help to differentiate it from other fluid collections. Hence, this is a useful additional imaging modality for the diagnosis of empyema after cranioplasty.

Adolescent↗

Prognostic significance of dysadherin expression in advanced colorectal carcinoma.

A novel glycoprotein, dysadherin, has an anti-cell - cell adhesion function through downregulating E-cadherin. In this study, we investigated the expressions of dysadherin and E-cadherin in 82 patients with stage II and III colorectal carcinomas to determine the correlation between the two molecules and the clinicopathologic features of each tumour. Dysadherin was not expressed in normal colorectal epithelium. Fifty-one per cent of tumours showed dysadherin immunopositivity in over 50% of cancer cells. Thirty-eight per cent of tumours showed reduced E-cadherin immunopositivity. The increased expression of dysadherin was significantly associated with lung metastasis (P=0.003). The increased expression of dysadherin had a significant impact on patient survival (P=0.0099 and 0.0036, log-rank test for overall and recurrence-free survival rate, respectively). Furthermore, tumour with increased expression of dysadherin and reduced expression of E-cadherin showed the worst prognosis (P=0.0043 and 0.0028, log-rank test for overall and recurrence-free survival rate, respectively). These results suggest that increased dysadherin expression is a significant indicator of poor prognosis for patients with advanced colorectal carcinoma.

Aged↗

A simple, yet accurate method for detecting and quantifying secretions from human minor salivary glands using the iodine-starch reaction.

The lack of published information about the minor salivary glands is due in part to the difficulties experienced in collecting and quantifying their secretions. In fact, no method exists for measuring their secretions that is both simple and accurate. This investigation examined the accuracy of our newly developed method (which simply employs the iodine-starch reaction) in 10 healthy non-medicated adults. A strip painted with a solution of iodine in absolute alcohol then with a fine starch powder mixed with castor oil was placed at a designated location on the lower-lip mucosa for 2 min to collect saliva. Black-stained spots of various sizes corresponding to the individual glands could be accurately visualized. After removal of the strip, the total stained area (mm2) was calculated by digitizing the spot areas using a computer system. The correlation coefficient (r) between known volumes of saliva and stain size was 0.995, indicating a close correlation. The correlation coefficient (r) between area values obtained in the first trial in each subject (Y) and the second (X; 10 min later) was 0.963, and the simple regression equation was close to Y=X, indicating good reproducibility. The mean flow rate microl/cm2 per min) obtained by converting mean total area to volume and thence to flow rate was 0.49+/-0.26, in good agreement with published values obtained by others. These results suggest that our newly developed method allows both the distribution and secretion rate of the minor salivary glands to be observed, and that it should be of practical value due to its simplicity, accuracy, and reproducibility.

Adult↗

Detection of cardiovascular risk factors by indices of obesity obtained from anthropometry and dual-energy X-ray absorptiometry in Japanese individuals.

OBJECTIVE: To determine the cut-off points of indices of obesity for detecting hypertension, dyslipidemia and diabetes mellitus in Japanese individuals. DESIGN: Cross-sectional study. SUBJECTS: A total of 2728 Japanese individuals (768 males and 1960 females, aged 20-79 y) who attended the Fukuoka Health Promotion Center, Japan for health check-up. MEASUREMENTS: Body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) were measured. Percentage fat mass (%FM), trunk fat mass (FM(trunk)) and trunk fat mass-leg fat mass ratio (FM(trunk)/FM(legs)) were obtained by dual-energy X-ray absorptiometry (DXA). Cardiovascular risk factors were determined by blood pressure, serum lipids, fasting blood glucose and hemoglobin A(1C). RESULTS: The cut-off points of BMI, WC and WHR were around 23.5 kg/m(2), 84 cm and 0.9 for males, and 22.5 kg/m(2), 72 cm and 0.8 for females. The cut-off points of %FM, FM(trunk) and FM(trunk)/FM(legs) were around 24%, 8 kg and 1.6 for males, and 35%, 9 kg and 1.4 for females. WHR and FM(trunk)/FM(legs) most accurately detected the risk factors. CONCLUSIONS: For Japanese individuals, the cut-off points for detecting cardiovascular risk factors are lower than the criteria by the World Health Organization. Indices of fat distribution detected the cardiovascular risk factors more accurately than those of overall adiposity. The accuracy of detecting the risk factors was comparable between the anthropometric indices and indices obtained by DXA.

Absorptiometry, Photon↗

Usefulness of heavily T(2) weighted magnetic resonance images for the differential diagnosis of parotid tumours.

OBJECTIVES: To evaluate the usefulness of heavily T(2) weighted (T2W) magnetic resonance (MR) images for the differential diagnosis of parotid tumours. METHODS: Conventional T2W and heavily T2W images obtained from 43 patients with parotid tumours were reviewed retrospectively. Tumours were classified pathologically into three types: pleomorphic adenoma (25 cases), Warthin's tumour (7 cases) and malignant tumour (11 cases). During interpretation of each MR image, special attention was paid to the homogeneity and signal intensity displayed by the solid portions of the tumours. RESULTS: Heavily T2W images could distinguish pleomorphic adenoma from Warthin's tumour and malignant tumours based on the homogeneity and signal intensity of the solid portions, whereas conventional T2W images could not. On conventional T2W images, neither homogeneity nor signal intensity differed significantly among these three tumour types. On heavily T2W images, malignant and Warthin's tumours appeared more homogeneous than pleomorphic adenoma (P<0.0061); signal intensity from pleomorphic adenoma was significantly different to signal intensity from malignant tumours (P<0.05) and Warthin's tumour (P<0.005). CONCLUSIONS: Heavily T2W MR images can be useful in distinguishing pleomorphic adenoma from Warthin's tumour and malignant tumours.

Adenocarcinoma↗

Adeno-associated virus vector-mediated gene transfer into dystrophin-deficient skeletal muscles evokes enhanced immune response against the transgene product.

Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscular disorder caused by a defect in the DMD gene. AAV vector-mediated micro-dystrophin cDNA transfer is an attractive approach to treatment of DMD. To establish effective gene transfer into skeletal muscle, we examined the transduction efficiency of an AAV vector in skeletal muscles of dystrophin-deficient mdx mice. When an AAV vector encoding the LacZ gene driven by a CMV promoter (AAV-CMVLacZ) was introduced, beta-galactosidase expression markedly decreased in mdx muscle 4 weeks after injection due to immune responses against the transgene product. We also injected AAV-CMVLacZ into skeletal muscles of mini-dystrophin-transgenic mdx mice (CVBA3'), which show ameliorated phenotypes without overt signs of muscle degeneration. AAV vector administration, however, evoked substantial immune responses in CVBA3' muscle. Importantly, AAV vector using muscle-specific MCK promoter also elicited responses in mdx muscle, but at a considerably later period. These results suggested that neo-antigens introduced by AAV vectors could evoke immune reactions in mdx muscle, since increased permeability allowed a leakage of neo-antigens from the dystrophin-deficient sarcolemma of muscle fibers. However, resident antigen-presenting cells, such as myoblasts, myotubes and regenerating immature myofibers, might also play a role in the immune response.

Adenoviridae↗

Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer.

BACKGROUND: The aim of this study was to assess the implications of positive peritoneal washing cytology for management of patients with potentially resectable pancreatic cancer. METHODS: Cytological examination of peritoneal washings was performed in 134 patients who underwent surgical resection for pancreatic adenocarcinoma. The clinicopathological findings and the relationship between cytology results (including cytomorphology) and survival were investigated. RESULTS: One hundred and fourteen patients (85 per cent) had negative cytology results (group 1). Excluding one patient with atypical cells, positive cytology results were obtained in 19 patients (14 per cent): 16 patients without macroscopic peritoneal metastases (group 2) and three patients with minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had significantly larger (P < 0.001) and more advanced (P = 0.022) tumours than those in group 1. However, there were no significant differences in postoperative cumulative survival rates between groups 1 and 2 (P = 0.347). Two patients in group 2 are long-term survivors (40 and 58 months). In cytomorphological analyses, the presence of clusters with ragged edges and isolated carcinoma cells can be considered to indicate a high risk of peritoneal recurrence. CONCLUSION: Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery.

Adenocarcinoma↗

Detection of genes expressed in primary colon cancers by in situ hybridisation: overexpression of RACK 1.

AIMS: The isolation of various genes that are expressed in a region specific manner is considered useful for research in molecular pathology. In situ hybridisation (ISH) was used in a screening procedure to isolate these genes efficiently, using colon cancer as a model. METHODS: Suppression subtractive hybridisation (SSH) between colon cancer tissue samples and corresponding non-cancerous tissues was performed. Genes showing high expression in the cancers were selected using macro-DNA array analysis. As a final screening procedure, conventional ISH was performed to isolate genes expressed specifically in colon cancers. RESULTS: Sixty nine clones were selected by SSH and macro-DNA array analyses. These clones were then analysed by ISH to examine their expression patterns. ISH screening revealed that all the clones screened showed more intense signals in colon cancers than in non-cancerous tissues. Among them, RACK 1, which is a protein kinase C receptor and a homologue of the G protein beta subunit, was expressed intensely in colon cancer cells. RACK 1 expression was evaluated in multiple samples by ISH, and the results confirmed that RACK 1 was universally overexpressed in cells of all 11 colon cancers examined. CONCLUSIONS: Many genes, including RACK 1, expressed in colon cancer cells can be isolated efficiently by this method, and their precise expression pattern can be evaluated. These results indicate that ISH is an excellent technique for systemic screening of genes expressed in a region specific manner.

Blotting, Northern↗

Cerebellar ataxia associated with heteroallelic ceruloplasmin gene mutation.

BACKGROUND: Aceruloplasminemia, an autosomal recessive disorder that affects human iron metabolism, is caused by mutation of the ceruloplasmin gene. Heterozygous individuals with a partial ceruloplasmin deficiency may have normal iron metabolism and no clinical symptoms. METHODS: The authors clinically characterized three Japanese patients from two families who had cerebellar ataxia with hypoceruloplasminemia from the fourth decade of life. Genetic analysis, restriction fragment length polymorphism analysis, and a pathologic study were performed. RESULTS: All three patients presented with cerebellar dysfunction that included relatively nondisabling gait ataxia and dysarthria, as well as hyperreflexia. Brain and abdomen MRI showed cerebellar atrophy and no low-signal intensities in the basal ganglia, thalamus, and liver. Direct mutational analysis excluded SCA-1, SCA-2, SCA-3, SCA-6, SCA-7, SCA-8, SCA-12, and DRPLA. The patients partially lacked serum ceruloplasmin, and the protein concentrations and ferroxidase activities ranged from 36% to 41% of the control values; moreover, they were heterozygous for a nonsense mutation of the ceruloplasmin gene (Trp858ter). Serum iron concentration and transferrin saturation were normal. At autopsy, pathologic and biochemical examinations showed marked loss of Purkinje cells, a large iron deposition in the cerebellum, and small depositions in the basal ganglia, thalamus, and liver. CONCLUSION: Cerebellar ataxia reflects the site of iron deposition. Being heterozygous for mutation of the ceruloplasmin gene may result in cerebellar ataxia.

Aged↗

Mice lacking serum amyloid P component do not necessarily develop severe autoimmune disease.

Serum amyloid P component (SAP) is a major acute-phase reactant in mice. Recently, it was reported that SAP-deficient mice spontaneously developed anti-nuclear antibodies and severe glomerulonephritis. Because the SAP-deficient mice we generated display no obvious phenotypic abnormalities, we investigated whether our SAP-deficient mice would also spontaneously develop autoimmune responses. In accordance with the report, our mice produced high titers of anti-nuclear antibody but did not develop severe glomerulonephritis. On the other hand, it was recently reported that SAP bound to gram-negative bacteria via lipopolysaccharide (LPS) prevented LPS-mediated activation of a classical complement pathway. Thus, we asked if SAP-deficient mice would show altered responses to an intraperitoneal injection of LPS from Salmonella typhimirium. SAP-deficiency did afford resistance to lethality induced by high-dose LPS. Our experiments clearly showed that contrary to documented data, SAP-deficient mice do not develop serious autoimmune disease and we suggest that SAP has a critical role in LPS toxicity.

Animals↗

Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain.

Neural stem cells, which differentiate into neurons and glia, are present in the ventricular zone of the embryonal brain. The precise mechanism by which neural stem cells are maintained during embryogenesis remains to be determined. Here, we found that transient misexpression of the basic helix-loop-helix genes Hes1 and Hes5 keeps embryonal telencephalic cells undifferentiated although they have been shown to induce gliogenesis in the retina. These telencephalic cells later differentiate into neurons and astroglia when Hes expression is down-regulated, suggesting that Hes1- and Hes5- expressing cells are maintained as neural stem cells during embryogenesis. Conversely, in the absence of Hes1 and Hes5, neural stem cells are not properly maintained, generating fewer and smaller neurospheres than the wild type. These results indicate that Hes1 and Hes5 play an important role in the maintenance of neural stem cells but not in gliogenesis in the embryonal telencephalon.

Animals↗

Multipeptide-metalloporphyrin assembly on a dendrimer template and photoinduced electron transfer based on the dendrimer structure.

To construct an artificial photosynthetic system, peptide dendrimers [n-(X-HLY)PAMAMs: X = R, E; Y= L, F; n=4, 8, 16, 32 and 64 segments], in which amphiphilic alpha-helix peptides (X-HLY: R-HLL, E-HLL and R-HLF) were introduced at the end groups of polyamidoamine dendrimers (PAMAMs), were designed and synthesized. The peptide dendrimers 64-(X-HLY)PAMAMs are novel synthetic biopolymers with an enormous molecular weight, about 160 kDa, and with a regulated amino acid sequence and three-dimensional conformation. The peptide dendrimers bound Fe(III)- or Zn(II)-mesoporphyrin IX per two alpha-helices; this afforded a multimetalloporphyrin assembly similar to the natural light-harvesting antennae in photosynthetic bacteria. Circular dichroism studies and peroxidase activity measurements revealed that metalloporphyrins were coordinated to the peptide dendrimers in a regulated manner and packed more densely with the growth of the dendrimer generation. Fluorescence quenching and photoreduction studies with methylviologen demonstrated that the photoinduced electron-transfer function with the peptide dendrimer-multi-Zn-MP was accomplished more effectively as the dendrimer generation increased. Thus, the three-dimensional assembly of metalloporphyrins and peptides in the dendrimer was an effective module for light-harvesting antennae in an artificial photosynthetic system.

Amino Acid Sequence↗

Tandem transesterification and intramolecular cycloaddition of alpha-methoxycarbonylnitrones with chiral acyclic allyl alcohols: systematic studies on the factors affecting diastereofacial selectivity of the cycloaddition.

Factors affecting the stereochemical course of the intramolecular cycloaddition of intermediary alpha-allyloxycarbonylnitrone resulting from transesterification of alpha-methoxycarbonylnitrones 1a-d with chiral allyl alcohols 5 or 6 were investigated systematically. It was found that the factors of diastereofacial selection are highly dependent on the geometries of the allyl alcohols. In the cases where primary or secondary chiral (Z)-allyl alcohols are used, A(1,3)-strain arising from the chiralities in the (Z)-nitrone transition states of the intramolecular cycloaddtion is the most important factor. In contrast, in the case of the reaction using chiral nitrones 1c,d and (E)-allyl alcohols, steric interaction between the chiral N-substituent and the trans substituent of the olefin moiety in the intermediate is dominant. These aspects were applied to geometry-differentiated cycloaddition using a mixture of (E)-5 and (Z)-5. As a typical example, treatment of bulky 1b with a 1:1 mixture of (E)-5 and (Z)-5 in the presence of a catalytic amount of TiCl(4) and MS 4A gave 7b as the predominant product among four possible products.

Journal Article↗

Maternal germinal mosaicism of X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by abnormalities in tyrosine kinase (BTK), and is characterized by a deficiency of peripheral blood B cells. We studied cytoplasmic expression of BTK protein and analyzed the BTK gene (BTK) in peripheral blood mononuclear cells from two siblings with XLA and additional family members. Cytoplasmic expression of BTK protein in monocytes was not detected in either patient with XLA. A single base deletion (C563) in BTK-exon 6, which encodes the TH domain, was identified in both XLA patients. However, normal cytoplasmic expression of BTK protein in monocytes was detected in their mother without any BTK mutation. These results strongly suggest germinal mosaicism in the mother.

Agammaglobulinaemia Tyrosine Kinase↗

Palladium-catalyzed allylic alkylation using chiral hydrazones as ligands.

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (4) with a dimethyl malonate-BSA-LiOAc system and its derivatives has been successfully carried out in the presence of a new chiral hydrazone ligands such as 2-(diphenylphosphino)benzaldehyde SAMP hydrazone (DPPBA-SAMP) (3a) in high yields with high enantioselectives.

Journal Article↗