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Biomedical subjects

A Ito

Publications and source records attributed to A Ito.

At least 217 records · Page 12Linked to original sources

Prader-Willi syndrome in a child with XYY.

We report a 26-month-old boy with XYY syndrome, with the complication of Prader-Willi syndrome (PWS) due to uniparental maternal disomy of chromosome 15. To our knowledge, this is the first case of XYY syndrome and PWS. Clinical findings were fully compatible with the diagnostic criteria for PWS. Molecular analysis revealed a maternal heterodisomy of chromosome 15, indicating that non-disjunction of chromosome 15 had occurred at maternal meiosis I, and that the non-disjunction of chromosome Y and of chromosome 15 had occurred independently.

Child, Preschool↗

Involvement of transporter associated with antigen processing 2 (TAP2) gene polymorphisms in hepatitis C virus infection.

BACKGROUND & AIMS: Transporter associated with antigen processing (TAP) has essential roles in the antigen-presenting systems, translocating antigenic peptides from the cytosol into the endoplasmic reticulum. The aim of this study was to clarify whether TAP polymorphisms are involved in hepatitis C virus (HCV) infection. METHODS: The 145 HCV-infected Japanese patients examined in this study were categorized into two groups: 36 carriers with persistently normal alanine transaminase (ALT) values and 109 patients with chronic liver disease (CLD). TAP2 gene phenotypes were determined by means of polymerase chain reaction-restriction fragment length polymorphism, and their frequencies were compared between the two groups. RESULTS: Frequencies of TAP2*0101, *0102, and *0201 were not different between the two groups. However, TAP2*0103 frequency in carriers with normal ALT levels was significantly higher than that in patients with CLD (44% vs. 16%; P = 0.00064, Pc < 0.005). Although the TAP2*0103 allele was tightly linked with class II DRB1*1302-DQB1*0604 haplotype in this study, the TAP2*0103 frequency in the normal ALT group was also significantly higher than that in the CLD group even in DRB1*1302-DQB1*0604-negative patients (31% vs. 10%; P = 0.0076, Pc < 0.05). CONCLUSIONS: These findings suggest that TAP2*0103 may be closely associated with low serum ALT activity in HCV-infected Japanese patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Renal hemodynamics in Otsuka Long-Evans Tokushima fatty rat, a model rat of spontaneous non-insulin-dependent diabetes mellitus with obesity.

Renal hemodynamic features in obese non-insulin-dependent diabetic rats remain unknown. We investigated renal hemodynamic and morphologic changes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats at the age of 5 and 10 months compared with age-matched lean nondiabetic control rats (LETO). OLETF rats showed obesity compared with age-matched LETO rats. Hyperglycemia was mild in 5-month-old OLETF rats and moderate in 10-month-old OLETF rats. The absolute value for glomerular filtration rate (GFR) was significantly higher in OLETF rats than in age-matched LETO rats at the age of 5 and 10 months. Ten-month-old OLETF rats had significantly higher absolute values for renal plasma flow (RPF) than age-matched LETO rats but not 5-month-old OLETF rats. Stepwise multiple regression analysis revealed that body weight was a powerful determinant of GFR and RPF. When factored for body weight, no difference in GFR was demonstrated between 5-month-old OLETF and LETO rats, whereas 10-month-old OLETF rats still had significantly higher GFR and RPF than age-matched LETO rats. Renal hypertrophy was demonstrated in both 5- and 10-month-old OLETF rats even when factored for body weight. Glomerular volume was significantly increased in 10-month-old OLETF rats, but the ratio of glomerular volume to body weight was not different among the groups. Both absolute value for glomerular capillary length free from mesangial area and the value factored for glomerular area were significantly longer in OLETF rats than in age-matched LETO rats. Mesangial matrix expansion was remarkable in 10-month-old OLETF rats, and the glomerular sclerosis index was significantly higher in 10-month-old OLETF rats than in age-matched LETO rats. Stepwise multiple regression analysis revealed that body weight, hemoglobin A1c, and hypertriglyceridemia were powerful determinants for kidney weight and glomerular volume. These data suggest that renal hyperfiltration and hypertrophy observed in 10-month-old OLETF rats are related to diabetic metabolic disorders and that obesity-related conditions may be involved in the renal hemodynamic and morphologic features in OLETF rats.

Animals↗

Human Taenia in severe combined immunodeficiency (SCID) mice.

A rodent model for the development of the larval stages of human taeniid tapeworms would help advance immunodiagnosis in human and domestic animals and vaccine development for cysticercosis cellulosae or bovis in domestic animals. Here, Akira Ito and Mamoru Ito review recent results demonstrating the potential of the severe combined immunodeficiency (SCID) mouse for supporting development of the larval stages of Taenia saginata asiatica, T. saginata and T. solium.

Animals↗

Computerized assessment of the mastoid air cell system.

There have been many arguments on the development of pneumatization of temporal bone. However, a technique for direct volume measurement from high resolution computed tomography has never been reported. The aim of this paper is to develop a technique by using digital image processing to measure the volume of the mastoid air cell system. Forty three ears of 26 healthy subjects (13 males and 13 females) without a history of chronic or exudative otitis media, clear signs of Meniere's disease, severe sensorineural hearing impairment or malformation of temporal bone were eligible for enrolment in this study. Using a digital image processing technique, only the black air cells and tympanic cavity on the CT films are easily selected. Then, after image processing, only areas of these extracted black pneumatized parts are calculated. Consequently, the volume of pneumatized parts of temporal bone could be calculated separately as total volume and as partial volume that divided by several CT planes. The average volume of pneumatization in 43 temporal bones was 5.97 ml. However, since the volume of pneumatization in the temporal bone has traditionally been estimated by analyzing areas on X-ray films, the new method described in this study is significant for its ability to directly measure the volume of pneumatization in the temporal bone.

Adult↗

Effects of glutamine administration on liver regeneration following hepatectomy.

The intestine is now known to be an important site of protein production in the body, and glutamine (GLN) stimulates both secreted and non-secreted protein synthesis in the small bowel. The purpose of the present study was to evaluate the effect of GLN-supplemented parenteral nutrition on liver regeneration after hepatectomy. Animals were divided into two groups: a sham-operated control group (Group A) and a 70%-hepatectomy group (Group B). Postoperatively, one-third of the animals in each group were maintained on intravenous 10% glucose solution, on 10% glucose with 2% standard amino acid solution, or 10% glucose supplemented with 2% glutamine for 24 h. GLN administration after hepatectomy significantly promoted liver regeneration. In addition, assessment of amino acid metabolism showed that GLN administration activated GLN metabolism in the intestine and promoted alanine uptake by the remnant liver. This metabolic response also enhanced both secreted and non-secreted protein synthesis in intestinal epithelial cells, especially in cells isolated from the crypts. The proteins produced are important as a portal production factor for liver regeneration and intestinal cell proliferation. Bacterial and endotoxin translocation, on the other hand, was significantly reduced. Thus, the results of this study suggest that intravenous administration of GLN after hepatectomy significantly promoted liver regeneration.

Amino Acids↗

Neurocysticercosis case with a single cyst in the brain showing dramatic drop in specific antibody titers within 1 year after curative surgical resection.

We report on one Japanese case subject with neurocysticercosis (NCC) who had a single cyst in the brain and had undergone curative surgical resection. Pathological examination revealed that it was a cysticercus of Taenia solium. Serological examination of the pair serum samples just before and 1 year after surgery revealed that antibody responses against the glycoproteins, highly specific to NCC and detected in the serum sample just before surgery by both immunoblot and ELISA became negative within 1 year after the surgery. It is, therefore, strongly suggested that this case had a single cysticercus in his whole body and the presence of a single cysticercus was sufficient to evoke antibody responses against it.

Animals↗

Oncospheres of Taenia solium and T. saginata asiatica develop into metacestodes in normal and immunosuppressed mice.

Normal and immunosuppressed mice were infected with oncospheres of Taenia saginata asiatica and T. solium. Although normal ICR mice were not susceptible to these two parasites, cysticerci were recovered from the immunosuppressed ones following venous injection. For T. s. asiatica, immunosuppressed ICR mice had an infection rate of 12.5% and six cysticerci of this parasite were recovered from three males. After injection of T. solium oncospheres, a high infection rate of 57% was obtained and 23 cysticerci were collected from 13 male immunosuppressed ICR mice. The immunosuppressed C57 mice had the highest infection rate (100%) and cysticercus recovery rate (2.4%) for T. solium. The infection rate and cysticercus recovery rate in six normal C57 mice were 40% and 3% respectively. The immunosuppressed ICR, Balb/c and C3H mice were also susceptible to T. s. asiatica.

Animals↗

ELISA and immunoblot using purified glycoproteins for serodiagnosis of cysticercosis in pigs naturally infected with Taenia solium.

The establishment of reliable serological methods for cysticercosis in pigs is important for the surveillance, control and prevention of taeniosis/cysticercosis in humans as well as in pigs to prevent economic loss. Both ELISA and immunoblot using glycoproteins (GPs) purified by a single step of preparative iso-electric focusing, which are highly useful for human cysticercosis, have been applied for a serological study in pigs naturally infected with Taenia solium. All sera from pigs showed similar responses to those in human cysticercosis. Therefore, it is expected that both ELISA and immunoblots using GPs would be useful in differentiating infected pigs from uninfected ones.

Animals↗

1',2',3',4'-tetradehydrotubulosine, a cytotoxic alkaloid from Pogonopus speciosus.

Bioassay-guided phytochemical investigation of the stems of Pogonopus speciosus, using human oral epidermoid carcinoma (KB) cells as a monitor, led to the isolation of a novel alkaloid, 1',2', 3',4'-tetradehydrotubulosine (1), along with tubulosine (2) and psychotrine (3) as bioactive constituents. The structure of the novel compound was elucidated through 1D- and 2D-NMR spectroscopic methods. Alkaloids 1 and 3 showed weak cytotoxic activity against a panel of human cancer cell lines, with the potency of these compounds being markedly less than that of tubulosine (2).

Alkaloids↗

Enhancement of membrane-type 1-matrix metalloproteinase (MT1-MMP) production and sequential activation of progelatinase A on human squamous carcinoma cells co-cultured with human dermal fibroblasts.

Matrix metalloproteinase 2 (MMP-2)/gelatinase A plays an important role in tumour invasion and metastasis. Since MMP-2 is secreted as an inactive form (proMMP-2) from tumour and neighbouring stroma cells, the activation process is necessary to express the enzymic activity for degradation of extracellular matrix components. We herein reported that the activation of proMMP-2 was induced in human squamous carcinoma cells co-cultured with normal human dermal fibroblasts. When A431 cells were co-cultured with human fibroblasts at various cell ratios, 72-kDa proMMP-2 was converted to a 62-kDa active form through the appearance of a 64-kDa intermediate. The activation of proMMP-2 by co-culture was also observed in other carcinoma cell lines, HSC-4 and SAS, but not in normal human keratinocytes. We characterized by in vitro invasion assay that A431 cells in co-culture preferentially invaded through Matrigel and the increased invasive activity was inhibited by exogenously adding tissue inhibitor of metalloproteinases 2. The augmented proMMP-2 activation by co-culture was achieved by the increase in membrane type 1-MMP (MT1-MMP) production along with that of its mRNA level. The predominant appearance of MT1-MMP was immunologically observed in A431 cells, but not human fibroblasts of the co-culture. Furthermore, epidermal growth factor (EGF) enhanced the co-culture-mediated proMMP-2 activation by increasing the production and gene expression of MT1-MMP, and thereby tumour invasive activity was further augmented. These results suggest that the cell-cell contact between carcinoma cells and normal fibroblasts enhances the production of MT1-MMP followed by sequential activation of proMMP-2 on the tumour cell surface, which may be closely implicated in tumour invasion in vivo.

Carcinoma, Squamous Cell↗

Higher susceptibility to apoptosis following ultraviolet B irradiation of xeroderma pigmentosum fibroblasts is accompanied by upregulation of p53 and downregulation of bcl-2.

Apoptosis plays an important part as a defence mechanism in eliminating damaged cells. Among the complex factors which regulate apoptosis, the p53 tumour suppressor protein which is induced by DNA damage has been suggested to play a crucial part. Cells from xeroderma pigmentosum (XP) patients, which are defective in nucleotide excision repair, express higher levels of p53 and are highly susceptible to cell death after ultraviolet (UV) irradiation. To examine the relationships between DNA damage, p53 and apoptosis, normal and XP group A fibroblasts were exposed to UVB, and expressions of molecules involved in apoptosis were examined. Apoptosis of XP and normal cells was clearly detected at 48 h after irradiation with UVB at doses of 5 and 40 mJ/cm2, respectively. Cells were positive by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) staining under these exposure conditions. At 6 h after irradiation, p53 protein expression was induced in normal and XP cells at minimal doses of 10 and 2.5 mJ/cm2, respectively. Bcl-2 protein, an inhibitor of apoptosis, was downregulated prior to cell death following UVB exposure at doses that induced apoptosis in both cell types. These results suggest that DNA damage due to UVB induces apoptosis by upregulating proapoptotic molecules such as p53, and by downregulating anti-apoptotic molecules such as Bcl-2.

Apoptosis↗

The significance of resections for residual masses after chemotherapy in metastatic testicular tumors.

BACKGROUND: After chemotherapy for metastatic testicular tumors, masses may remain, often in the metastatic sites. This study analyses the role of resections for the residual masses. METHODS: Seventy-seven patients with advanced (stage II, III) testicular tumors were treated. Of these, 38 patients, including eight with seminoma and 30 patients with non-seminomatous germ cell tumors, underwent resection of residual masses after chemotherapy and have been followed for a median of 41.5 months (range 2-138) after the resection. RESULTS: Residual masses were necrosis/fibrosis in 19 patients, mature teratoma in 11 and cancer in eight. The ratio of cancer in stage III (41.2%) was significantly higher than that in stage II (4.8%). Ten of 38 (26.3%) patients experienced recurrences in sites other than the resected sites, and five of 10 patients have died of cancer. Most recurrences (80%) occurred within two years. Recurrences after resection were detected in 4.8% of stage II patients, 52.9% of stage III, 16.7% of necrosis/fibrosis and mature teratoma, and 62.5% of cancer. The survival rate of patients with cancer was significantly lower in spite of adjuvant chemotherapy after surgery. CONCLUSIONS: Resection for residual masses after chemotherapy in metastatic testicular tumors was useful in confirming the tissue and in controlling the metastatic sites. Recurrences were often found in patients with cancer in the residual mass and the prognosis of patients with cancer was poor, therefore the development of more effective therapy for patients with cancer is required to improve the prognosis.

Adolescent↗

Enhanced expression of melanocortin-1 receptor (MC1-R) in normal human keratinocytes during differentiation: evidence for increased expression of POMC peptides near suprabasal layer of epidermis.

Immunohistochemical staining of human skin specimen showed the stronger localization of proopiomelanocortin peptides near the suprabasal layer of the epidermis, where keratinocytes are mostly differentiated. To test the possibilities of whether the production of proopiomelanocortin peptides or their receptor-binding activity or both is increased during differentiation of keratinocytes, we treated the cells in culture with Ca2+ to induce their differentiation. The production of proopiomelanocortin peptides and its gene expression were not induced significantly, but the binding ability of melanocortin receptor, as well as its gene expression were stimulated by Ca2+. Ultraviolet B irradiation, an inducer of differentiation, stimulated both proopiomelanocortin production and melanocortin receptor expression. These data show that normal human keratinocytes express melanocortin receptor similar to melanocytes, and that it is induced during differentiation.

Adrenocorticotropic Hormone↗

Changes in thyroid function during development of thyroid hyperplasia induced by kojic acid in F344 rats.

To clarify the mechanism of tumorigenesis by kojic acid (KA), dose and time dependence of iodine uptake in the thyroid gland and serum thyroid stimulating hormone (TSH) and thyroid hormone levels were investigated in F344 rats fed a diet containing 2% KA. After 4 weeks, thyroid hyperplasia was apparent in males, associated with a decrease in (125)I uptake into the thyroid gland to only 3% of that in controls. The serum triiodothyronine (T(3)) and thyroxine (T(4)) levels dropped to 0.36 ng/ml, 1.7 micrograms/dl from the initial values of 0.61 ng/ml, 4.0 micrograms/dl and TSH increased seven times to 15 ng/ml. In females, the effects on thyroid weight and (125)I uptake were less prominent, although the changes in serum T(3), T(4) and TSH levels were similar to those in males. Time-dependent changes in serum T(3), T(4) and TSH levels correlated with the inhibition of iodine uptake in the thyroid. Inhibition of organic iodine formation was only observed after 3 weeks treatment. On return to the control diet, normal serum T(3), T(4) and TSH levels became evident within 48 h in both sexes. These data suggest that KA interrupts thyroid function, primarily by inhibiting iodine intake, consequently causing a decrease in serum T(3) and T(4). Increased TSH from the pituitary gland in turn stimulates thyroid hyperplasia, which is reversible on withdrawal of KA.

Animals↗

Pre-operative chemoradiation therapy with 5-fluorouracil and low-dose daily cisplatin for esophageal cancer: a preliminary report.

BACKGROUND: A combination of chemotherapy and radiotherapy (chemoradiation therapy; CRT) has recently been developed to improve the survival of esophageal cancer patients. However, the optimal choice of chemotherapeutic agents and their doses, as well as chemotherapy and radiotherapy regimens, remain unclear. METHODS: Based on recent advances in knowledge on the radiosensitizing and biochemical modulation effects of chemotherapeutic agents, we have recently developed concurrent CRT which consisted of continuous 5-fluorouracil (5FU) administration (600 mg/m2/day, days 1-5) combined with a low dose of daily cisplatin administration (10 mg/m2/day, days 1-5, and 5 or 10 mg/m2/day, days 8-12 and 15-19) before each fraction of radiation (2 Gy each). To evaluate the efficacy and safety of our concurrent CRT, 10 esophageal cancer patients received one or one and a half courses of the CRT. RESULTS: All patients tolerated and completed a full course of the CRT. The effectiveness of the CRT on the primary tumor included pathologically or endoscopically complete responses in three patients (30%), partial response in five (50%), no response in two (20%) and tumoral downstaging (T-classification) in five (50%). Grade 2 and Grade 3 toxicity, seen in six patients, did not affect surgical operation. No patients showed CRT-related deaths. Eight patients (80%) underwent resection with no operative mortality. Of these, two patients (25%) showed pathologically or endoscopically complete responses, and four (50%) showed partial response. Three patients died of cancer after resection. The two inoperable patients showed a pathologically complete response and partial response, respectively. They were relieved of their cancer-related complaints and were living without hospitalization at the time of this analysis. CONCLUSIONS: These results suggest that the concurrent CRT based on the theoretical backgrounds is effective and has acceptable toxicities with maintaining its efficacy for the treatment of esophageal cancer patients.

Aged↗

Analysis of recognition elements for mitochondrial processing peptidase using artificial amino acids: roles of the intervening portion and proximal arginine.

We recently demonstrated, using synthetic peptides modeled on the extension peptide of malate dehydrogenase, that amino acid residues present at the proximal and distal positions relative to the cleavage site are critical determinants for the recognition of substrates by mitochondrial processing peptidase [Niidome et al. (1994) J. Biol. Chem. 269, 24719-24722). While the proximal arginine is unexceptionally located at the -2 position, the position of the distal residue varies among mitochondrial precursor proteins. Between the proximal and distal residues, proline and/or glycine are present in most mitochondrial precursor proteins, and they are considered to play a role in the specific recognition of a substrate by the peptidase. To elucidate the role of the intervening portion, we introduced a non-natural amino acid [2-(2-aminoethoxy)acetic acid] between the distal and proximal residues. We also analyzed the functional elements in the proximal arginine by replacing the residue with various arginine or lysine analogs. The results of kinetic studies indicated that the intervening portion should be flexible for efficient processing, and that the guanidino group of the proximal arginine is recognized by the peptidase through hydrogen and ionic bonds.

Amino Acid Sequence↗

Cystic echinococcosis in a Jordanian patient: albendazole in a short-term immigrant.

With an ever increasing number of international travelers, physicians should be aware of the diseases that have rarely been encountered in their home countries. Cystic echinococcosis (CE) caused by Echinococcus granulosus is seldom seen in Japan despite frequent occurrence of the other type of echinococcosis, alveolar echinococcosis (AE) caused by E. multilocularis, in its northern parts. However, CE is prevalent in many parts of the world including the United Kingdom, Mediterranean basin, Middle East, South America, and Australia, and is supposed to be resurgent in several parts of the world. The disease is acquired by the oral ingestion of the eggs of E. granulosus passed into the feces of several definitive host animals carrying tapeworms, mostly dogs. These definitive hosts are infected by cannibalizing intermediate host animals including sheep and cattle whose livers and/or lungs are affected by cystic lesions that contain protoscoleces. In endemic areas the diagnosis of CE is not considered to be complicated; typical morphological features composed of cysts as revealed by ultrasonography and/or computerized tomography (CT) scan. The diagnosis is also aided by serological methods detecting serum antibodies. However, imaging procedures show a variety of features that could often lead to misdiagnosis as other diseases. Moreover, serological assays are sometimes difficult to interpret because of their incomplete sensitivities and specificities. Hence, a comprehensive understanding of a spectrum of imaging features and the application of serological methods with better sensitivities and specificities are indispensable. The mainstay of treatment of the disease is still surgical removal of cysts that has the potential to lead to a complete cure. Recently, the less invasive method PAIR (Puncture of cysts percutaneously, Aspiration of fluid, Introduction of protoscolicidal agent, and Reaspiration) was introduced with considerable success, and could be a promising alternative to surgery. Lastly, medical treatment with oral mebendazole or albendazole, especially the latter, can be beneficial not only as a adjunctive to surgery or PAIR, but as a sole treatment in cases in which invasive methods are not indicated. Here we report a Jordanian patient with CE whose diagnosis was substantiated by a novel immunoblot assay and who showed a rapid improvement during albendazole therapy.

Adult↗