Biomedical subjects

A Sato

Publications and source records attributed to A Sato.

At least 145 records · Page 8Linked to original sources

PubMed2000

Migratory patterns of thoracic duct lymphocytes into bronchus-associated lymphoid tissue of immunized rats.

Lymphocytes continuously circulate between the bloodstream and lymphoid organs, and their migration into lymphatic tissues presumably occurs through selective mechanisms. Although bronchus-associated lymphoid tissue (BALT) is known as an inductive tissue of the common mucosal immune system, little is known about how effectively the lymphocytes in the blood vessels migrate into the BALT, thereby enabling the BALT to act as an effector tissue in the immunologic responses of the lungs. To analyze whether or not thoracic duct lymphocytes (TDL) from immunized and nonimmunized rats possess different migratory patterns to the BALT, 5-(6)-carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled TDL were injected into rats with BALT hyperplasia that was produced by intratracheal administration of TNP-KLH, and then the number of labeled cells in the BALT were examined by immunohistochemical methods. We studied the following three groups at 12 h after the injection: group A, intraintestinally immunized donors and intratracheally immunized recipients; group B, nonimmunized donors and intratracheally immunized recipients; group C (control group), nonimmunized donors and nonimmunized recipients. Time course studies 0.5, 4, 12, and 24 h after the injection were done in groups A and C. In a cytokinetic study, larger numbers of CFSE-labeled lymphocytes were found at 12 h and 24 h in group A than in group C. At 12 h after the injection, the absolute number of CFSE-labeled lymphocytes per BALT was significantly higher in group A than in group B (p < 0.05), and was lowest in group C. Histologically, there was a marked proliferation of high endothelial venules (HEV), with findings of adhesion and influx of lymphocytes inside the HEV in group A. These observations indicate that the immunized BALT actively recruits immunized TDL through a specific mechanism of lymphocyte-endothelium recognition in HEV, which partially explains the process of BALT development as an effector tissue for local immunity.

Animals↗

PubMed2000

Isolation and characterization of simian immunodeficiency virus variants that are resistant to nonnucleoside reverse transcriptase inhibitors.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) act quite specifically on human immunodeficiency virus type 1 (HIV-1). In general, they are not effective on human immunodeficiency virus type 2 (HIV-2) or simian immunodeficiency virus (SIV). Only SIV strains from African green monkeys are sensitive to several NNRTIs. Here we isolated NNRTI- and 3TC-resistant SIVagm variants. Viruses resistant to delavirdine contained V112I and M231I substitutions, while those resistant to 3TC contained a M 185I substitution. These amino acids are highly conserved in HIV-1, HIV-2, SIVmac and SIVagm, and the M184I (M185I in SIVagm) substitution was observed in 3TC-resistant HIV-1 and SIVmac. The roles of the observed mutations in NNRTI-resistance of SIVagm and HIV-1 were further confirmed by site-directed mutagenesis. The present results have provided a new insight into the common mechanism of sensitivity of HIV- 1 and SIVagm to NNRTIs.

Amino Acid Sequence↗

PubMed2000

Importance of hypercoagulability over hyperglycemia for vascular complication in type 2 diabetes.

To critically evaluate the relative importance of coagulation abnormalities over other clinical variables for micro- and macrovascular diabetic complications, prothrombin fragment (F1+2), thrombin-antithrombin III complex (TAT), fibrin degradation product d-dimer, and alpha2 plasmin inhibitor complex were determined in 101 stable, relatively well controlled patients with Type 2 diabetes (the mean HbA1c, age and duration of diabetes, 7.1%, 61 and 7.5 years, respectively). First, incidence and severity of diabetic micro- and macroangiopathies were progressively increased with the severity of coagulation abnormalities. Next, correlation of the four values with the presence of micro- and macrovascular complications, respectively, was analyzed by the multiple logistic regression analysis, with the inclusion of other variables such as age, duration of diabetes, HbA1c, blood pressure, and urinary albumin excretion. With the presence of microangiopathies, F1+2 and systolic blood pressure were significantly related, with the relationship being very strong for the former (P=0.003) and weak for the latter (P=0.035). On the other hand, with the presence of macroangiopathies, F1+2 (P=0.003), TAT (P=0.002), duration of diabetes (P=0.015), and age (P=0.013) were related. Other clinical variables were not significantly related with the presence of complications. Coagulation and fibrinolytic abnormalities are stronger determinants of the presence of diabetic vascular complications than other clinical variables including the degree of glycemia, in stable, relatively well controlled patients with Type 2 diabetes.

Adult↗

PubMed2000

Cloning and expression pattern of a Xenopus pronephros-specific gene, XSMP-30.

The first step in kidney development is the formation of the pronephros which is derived from mesoderm. Xenopus is an appropriate model to study this process since the pronephros can be efficiently induced in animal cap explants by treatment with activin and retinoic acid (RA). Using this in vitro system, we isolated a Xenopus homologue of SMP-30 (Senescence marker protein-30), which is a Ca(2+)-binding protein that is highly conserved in vertebrates. This gene, termed XSMP-30, was found to be selectively expressed in pronephric tubules from the late tadpole stage, by whole mount in situ hybridization. Furthermore XSMP-30 was expressed in animal caps treated with both activin and RA, a condition in which the pronephros is formed in vitro. These data indicate that XSMP-30 is a specific marker for the pronephros.

Activins↗

PubMed2000

Galloylglucosides from berries of Pimenta dioica.

Three new galloylglucosides, (4S)-alpha-terpineol 8-O-beta-D-(6-O-galloyl)glucopyranoside (1); (4R)-alpha-terpineol 8-O-beta-D-(6-O-galloyl)glucopyranoside (2), and 3-(4-hydroxy-3-methoxyphenyl)propane-1,2-diol 2-O-beta-D-(6-O-galloyl)glucopyranoside (3), were isolated from the berries of Pimenta dioica together with three known compounds, gallic acid (4), pimentol (5), and eugenol 4-O-beta-D-(6-O-galloyl)glucopyranoside (6). The structures of 1-3 were elucidated on the basis of MS and NMR spectral data and enzymatic hydrolysis. These galloylglucosides (1-3, 5, and 6) showed radical-scavenging activity nearly equivalent to that of gallic acid (4) against 1,1-diphenyl-2-picrylhydrazyl radical.

Cyclohexane Monoterpenes↗

PubMed2000

1H-NMR determination of the solution structure and absolute configuration of FR134043, a novel inhibitor of human leukocyte elastase.

FR134043 is a semisynthetic disulfonated derivative of the natural product FR901277, is isolated from the culture filtrate of Streptomyces resistomicificus and has potent inhibitory activity against human leukocyte elastase. Although the chemical structure of FR134043 was determined to be a unique bicyclic peptide-like compound consisting of seven amino acids by using several spectroscopic analytical methods, the chiralities of three centers were unknown. A simple simulated annealing protocol to determine the structure was applied to the eight possible stereoisomers, and the one that best satisfied the NOE distance constraints was determined to be the true stereoconfiguration of FR134043. The solution structure showed that all Calpha atoms existed in the L configuration and six of the seven side chains were located towards the outside of the bicyclic framework, even though most of them are highly hydrophobic moieties. The simulated annealing calculation described here is a frequently used method for the determination of the solution structure of peptides or small proteins. We show here that it is also applicable to the determination of the absolute configuration of macrocyclic compounds produced from natural sources.

Heterocyclic Compounds↗

PubMed2000

Three-dimensional solution structure of a disulfide bond isomer of the human insulin-like growth factor-I.

The solution structure of a disulfide bond isomer of human insulin-like growth factor-I (IGF-I) was determined using homonuclear NMR methods. A total of 292 interatomic distance constraints, including 12 related to the disulfide bridges, was used in the distance geometry calculations. The determined structures contain two helical rods corresponding to the sequence regions, Ala8-Cys18 and Leu54-Cys61. Comparison with the previously determined structure of native human IGF-I revealed partial correspondence of the secondary structure (helices I: Ala8-Cys18 and helices III: Leu54-Cys61) and internal packing. Helix II in native human IGF-I (residues Gly42-Cys48) is disrupted in the isomer. A similar relationship has been described between the structure of native insulin and a homologous disulfide isomer, suggesting that these alternative folds represent general features of insulin-like sequences. In each case the precision of the distance geometry ensemble is low due in part to resonance broadening and a paucity of NOEs relative to other globular proteins of this size. These observations suggest that tertiary structure of the isomer is not highly ordered. Comparison of the biological activities of native and the disulfide bond isomer of human IGF-I highlight the importance of Tyr24, Phe25, Phe49-Cys52 and Phe16 in binding to the IGF-I receptor or specific IGFBPs. The relationship of this proposed receptor-binding surface of human IGF-I to those of insulin is discussed.

Amino Acid Sequence↗

PubMed2000

Clear cell odontogenic tumor in the mandible: report of a case with duct-like appearances and dentinoid induction.

A case of clear-cell odontogenic tumor with unusual histological features is presented. A 61-year-old Japanese man was admitted because of swelling of the left premolar-molar region of the mandible. Radiological examination revealed a multilocular radiolucency with irregular margins. Histological examination of the resected specimen showed infiltrative proliferation of both clear and eosinophilic cells into the adjacent soft tissue without encapsulation, suggesting the malignant potential of the tumor. The tumor cells sporadically formed cystic lesions. In addition, several tumor cell nests showed duct-like characteristics, and many eosinophilic dentin-like structures were attached to the tumor cell nests, suggesting the potential for epithelial-mesenchymal induction. Histochemically, the clear tumor cells possessed cytoplasmic glycogen granules. Both clear and eosinophilic tumor cells showed positive immunoreactivities for cytokeratin 19, epithelial membrane antigen and filaggrin, indicating an odontogenic epithelial origin.

Dentin↗

PubMed2000

Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription.

At least eight inherited neurodegenerative diseases are caused by expanded CAG repeats encoding polyglutamine (polyQ) stretches. Although cytotoxicities of expanded polyQ stretches are implicated, the molecular mechanisms of neurodegeneration remain unclear. We found that expanded polyQ stretches preferentially bind to TAFII130, a coactivator involved in cAMP-responsive element binding protein (CREB)-dependent transcriptional activation, and strongly suppress CREB-dependent transcriptional activation. The suppression of CREB-dependent transcription and the cell death induced by polyQ stretches were restored by the co-expression of TAFII130. Our results indicate that interference of transcription by the binding of TAFII130 with expanded polyQ stretches is involved in the pathogenetic mechanisms underlying neurodegeneration.

Aged↗

PubMed2000

Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomes.

A novel mannosylated cholesterol derivative, cholesten-5-yloxy-N-(4-((1-imino-2-beta-D-thiomannosyl -ethyl)amino)bu tyl) formamide (Man-C4-Chol), was synthesized in order to perform mannose receptor-mediated gene transfer with liposomes. Plasmid DNA encoding luciferase gene (pCMV-Luc) complexed with liposomes, consisting of a 6:4 mixture of Man-C4-Chol and dioleoylphosphatidylethanolamine (DOPE), showed higher transfection activity than that complexed with 3beta[N-(N', N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol)/DOPE(6:4) and N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/DOPE(1:1) liposomes in mouse peritoneal macrophages. The presence of 20 mM mannose significantly inhibited the transfection efficiency of pCMV-Luc complexed with Man-C4-Chol/DC- Chol/DOPE(3:3:4) and Man-C4-Chol/DOPE(6:4) liposomes. High gene expression of pCMV-Luc was observed in the liver after intravenously injecting mice with Man-C4-Chol/DOPE(6:4) liposomes, whereas DC-Chol/DOPE(6:4) liposomes only showed marked expression in the lung. The gene expression with Man-C4-Chol/DOPE(6:4) liposome/ DNA complexes in the liver was observed preferentially in the non-parenchymal cells and was significantly reduced by predosing with mannosylated bovine serum albumin. The gene expression in the liver was greater following intraportal injection. These results suggest that plasmid DNA complexed with mannosylated liposomes exhibits high transfection activity due to recognition by mannose receptors both in vitro and in vivo. Gene Therapy (2000) 7, 292-299.

Animals↗

PubMed2000

Anti-HPA-5b-induced neonatal alloimmune thrombocytopenia: antibody titre as a predictor. Collaborative Study Group.

Anti-HPA-5b is the most commonly found platelet-specific antibody among pregnant women, but it does not cause severe fetal-neonatal alloimmune thrombocytopenia in the majority of affected infants. However, as the sequelae of the affected children may become severe, it is necessary to identify the risk factors for neonatal alloimmune thrombocytopenia. Of 21 354 consecutive pregnant women, 138 [0.65%; 95% confidence interval (CI) 0.54-0.75%], corresponding to 13.2% of the 1049 HPA-5b- women calculated by the gene frequency, were positive for anti-HPA-5b at the first trimester. Anti-HPA-5b was titrated in specimens obtained at the third trimester and antibody-positive women and their neonates were HPA-5 genotyped. Platelet counts in cord blood and 3 d after birth were assessed in the infants born to these mothers. Chi-square analysis showed no significant relationship between the titres of maternal antibody to HPA-5b and the number of pregnancies. There was a significant difference in platelet counts at d 3 between neonates who were compatible (267 x 109/l) or incompatible (220 x 109/l, P < 0.05) with maternal anti-HPA-5b. HPA-5b antibody titres >/= 64 were related to the development of thrombocytopenia (< 150 x 109/l) in neonates 1 d and 3 d after birth. A high titre (>/= 64) had a positive predictive value of 50% for thrombocytopenia 3 d after birth when the infant was HPA-5b+ and a negative predictive value of 100%. These results indicate that a high titre (>/= 64) of anti-HPA-5b is associated with a higher risk of neonatal thrombocytopenia, even if anti-HPA-5b-induced severe thrombocytopenia rarely develops.

Antigens, Human Platelet↗

PubMed2000

Oocyte activation induced by spermatids and the spermatozoa.

It has been reported that a sperm factor (SF) found in spermatozoa plays a critical role in fertilization. However, particulars of the oocyte-activating and Ca2+ oscillation (Ca-Os)-inducing abilities of this SF remain unknown. We examined these abilities of spermatids in mouse, hamster and human by a mouse test (injection of spermatids into mouse oocytes). In mice, the round spermatids (ROS), elongated spermatids (ELS) and spermatozoa activated 0%, 93% and 92% of the oocytes, respectively. ROS injection resulted in no Ca-Os (type C). ELS induced a normal oscillation (type A) at 0% and an abnormal oscillation (type B) at 94%. Mouse spermatozoa induced type A Ca-Os at 90%. For mice, oocyte-activating and Ca2+ oscillation-inducing ability arose in different phases of spermiogenesis. We also observed this differential timing for hamster spermatids. Hamster ROS activated 74% of oocyte (ELS: 90%, sperm: 86%). Human ROS activated 64% of oocytes (sperm: 100%), but only 35% of the oocytes showed type A Ca-Os. These results indicate that oocyte activation generally occurs between the ROS and ELS phases, although these phases differ among species. They also indicate that oocyte activation is not necessarily accompanied by Ca-Os. These findings suggest the existence of different thresholds at which the SF induces oocyte activation and Ca2+ oscillation, or of different factors that induce oocyte activation and Ca-Os. We found SF to be clinically impaired in 0.9% of ICSI patients. A combination of artificial oocyte activation and ICSI proved effective with such patients.

Animals↗

PubMed2000

A comparative clinical study of pneumonia by penicillin-resistant and -sensitive Streptococcus pneumoniae in a community hospital.

OBJECTIVE: This study aimed to determine the clinical difference of pneumonia between penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae. METHODOLOGY: Forty-nine cases in 46 patients of pneumococcal pneumonia were studied from December 1992 to May 1997. There were 24 cases (in 22 patients) of penicillin-resistant pneumococci (PRSP) pneumonia which were compared with 25 cases (in 24 patients) with penicillin-sensitive pneumococci (PSSP). RESULTS: Both the mean age and the underlying disease states did not differ between the two groups. However, hospital-acquired pneumonia and previous use of antibiotics were observed in eight (33.3%) and 12 (50.0%) patients in PRSP compared with three (12.0%) and two (8.0%) in PSSP, respectively. The clinical efficacy rate and bacteriological eradication rates were 87.5 and 87.5% in PRSP compared with 87.5 and 87.0% in PSSP, respectively. Minimum inhibitory concentration (MIC) of antibiotics against 30 pneumococcal isolates was examined, and 10 strains ranged from 0.10-0.78 microg/mL and five strains were more than 1.56 microg/mL against penicillin G, while the MIC showed higher resistance to other antibiotics except for the carbapenems. Serotyping of the isolates by antiserum revealed differences in the predominant types PRSP (19F) and PSSP (6A,9V) [corrected]. CONCLUSIONS: We must care for not only community-acquired infection but also nosocomial transmission of PRSP pneumonia. Most patients with infections due to PRSP tended to have a milder illness with a good outcome (no patient died). As such it appears that empiric therapy for pneumococcal pneumonia does not require modification from what is recommended at present. However, in patients with infection due to highly resistant strains, and who are not responding to conventional therapy should have their treatment modified according to subsequent susceptibility testing.

Anti-Bacterial Agents↗

PubMed2000

Antigen uptake and subsequent cell kinetics in bronchus-associated lymphoid tissue.

OBJECTIVE: Bronchus-associated lymphoid tissue (BALT) plays an important role in the immunological defence of airways. However, the mechanisms of BALT development, antigen sampling, and subsequent cell kinetics remain unclear. To clarify these chronological processes, we used a Pseudomonas aeruginosa-exposed mouse model. METHODOLOGY: In BALB/c and C57BL/6 mice, BALT development was induced by inhalation of heat-killed P. aeruginosa after sensitization with subcutaneous injection of P. aeruginosa in the presence of Freund's complete adjuvant. Subsequently, we chronologically killed these mice who had inhaled PKH26-labelled P. aeruginosa and examined bacterial transport using fluorescence microscopy. The distribution of interleukin-4-positive cells and interferon-gamma-positive cells was studied immunohistochemically. RESULTS: The degree of BALT hyperplasia was greater in sensitized mice than in non-sensitized mice and in BALB/c mice than in C57BL/6 mice. PKH26-labelled bacteria were found in BALT earlier in sensitized mice than in non-sensitized mice. Immunohistochemical studies revealed that interleukin-4-positive cells predominated over interferon-gamma-positive cells in the peripheral areas of lymphoid follicles. CONCLUSION: These results indicate that administered antigens are actively transported into BALT and that sensitized Th2 lymphocytes play an important role in forming and maintaining BALT.

Animals↗

PubMed2000

Long-term survivors after the resection of limited esophageal small cell carcinoma.

Patients with small cell carcinoma of the esophagus have a poor prognosis and have generally been treated by chemotherapy. However, all reported cases were at advanced stages. We need to establish an adequate treatment for patients with small cell carcinoma of the esophagus with invasion limited to the submucosal layer. In this paper, five cases of small cell carcinomas, which accounted for 2.8% of 180 surgically treated esophageal carcinomas, were reviewed for pathological findings, treatment, and outcome. Among three patients who had a small cell carcinoma of the esophagus with invasion limited to the submucosal layer, two patients survived for 7 and 9 years after surgery with no evidence of the disease. One of them was treated using surgery alone. Consequently, surgery may be considered as a possible choice of treatment for small cell carcinoma of the esophagus with invasion limited to the submucosa.

Adult↗

PubMed2000

Ataxic form of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

We reported a 64-year-old male with an eight-month history of gait disturbance and sensory impairment. The patient initially noticed unsteadiness of gait and numbness in his feet, and these symptoms progressed until he was unable to walk without assistance five months later. Vibratory sensation and position sense were markedly diminished, and deep tendon reflexes were absent in all extremities. Motor conduction velocities were slow with prolonged distal latencies, and sensory nerve action potentials (SNAP) were not elicited. Sural nerve biopsy revealed a mild loss of myelinated fibres and segmental demyelination. Cerebrospinal fluid showed normal cell count with protein 526 mg/dL. Anti-GM1, anti-GM2 and anti-GA1 antibodies in serum were positive. We diagnosed chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) presenting ataxia. Steroid therapy provided immediate improvement of symptoms and signs. This case suggests that CIDP should be considered as one of the potential causes of ataxic neuropathy.

Ataxia↗

PubMed2000

Higher incidence of diabetic nephropathy in type 2 than in type 1 diabetes in early-onset diabetes in Japan.

BACKGROUND: Whether the type of diabetes, race, and year and age of diagnosis affect the incidence of diabetic vascular complications is unknown. That both type 1 and type 2 diabetes occur in the young Japanese population prompted us to investigate whether the type of diabetes and the year of diagnosis are related to the incidence of nephropathy. METHODS: Of the 17,256 diabetic patients who visited the outpatient clinic at our diabetes center between 1965 and 1990, 1578 (9.1%) had early-onset diabetes (diagnosed before the age of 30); of these, 620 (39%) had type 1, and 958 (61%) had type 2 diabetes. The incidence of nephropathy was analyzed in the patients according to postpubertal duration and year of diagnosis. RESULTS: The cumulative incidence of nephropathy after 30 years of postpubertal diabetes was significantly higher (P < 0.0001) in type 2 diabetic patients (44.4%, 95% CI, 37.0 to 51.8%) than in type 1 diabetic patients (20.2%, 95% CI, 14.9 to 25.8%). The incidence of nephropathy among type 1 diabetic patients has declined during the past two decades, whereas it has not among type 2 diabetic patients. The rate ratio for type 2 diabetic patients diagnosed between 1980 and 1984 relative to type 1 diabetic patients diagnosed in the same period was 2.74 (95% CI, 1. 17 to 6.41). CONCLUSIONS: The incidence of nephropathy has declined in Japanese patients with type 1 but not in those with type 2 diabetes. In young Japanese patients, because of the higher incidence of nephropathy in type 2 diabetes and the higher prevalence of type 2 than type 1 diabetes, type 2 diabetes is likely the major cause of diabetic nephropathy.

Adolescent↗

PubMed2000

Mother-to-infant transmission of GB virus type C/HGV.

BACKGROUND: The potentially hepatotropic flavivirus-like virus, GB virus type C (GBV-C)/HGV, has been detected in a few patients with acute and chronic hepatitis and in a certain proportion of blood donors and recipients of blood or blood components. STUDY DESIGN AND METHODS: Sera from 2979 pregnant Japanese women were examined for the presence of GBV-C/HGV RNA by nested RT-PCR. Mothers who were positive for viral RNA and their 34 infants were followed and tested for infection. RESULTS: Of the 2979 women, 32 (1.1%) were positive for GBV-C/HGV RNA. Twenty-six (76.5%) of 34 babies born to these women were positive for the virus when first tested. A significantly higher titer of viral RNA was observed in mothers whose infants were infected than in those whose infants were uninfected (mean +/- SD, 10(6.3 +/- 0.9) vs. 10(4.6 +/- 0.9)/mL; p<0.001). Twenty-three (96%) of 24 babies born to mothers whose serum viral titers were 10(6) mL or more were infected with the virus. Infants delivered by elective caesarean section had a lower risk (OR, 0.13; 95% CI, 0.02-0.82) than those delivered vaginally or by emergency caesarean section. No other risk factors for mother-to-infant transmission were confirmed. CONCLUSIONS: GBV-C/HGV is frequently transmitted from mothers to infants in the general population. The most critical factor is the titer of viral RNA in the maternal serum. By the use of elective caesarean section in women with high titers of viral RNA, vertical transmission of the virus may be lessened.

Carrier State↗