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Biomedical subjects

J Sasaki

Publications and source records attributed to J Sasaki.

At least 127 records · Page 7Linked to original sources

[Apolipoprotein A-I mutations and low high density lipoproteinemia].

Mutations in the apo A-I gene which affect apo A-I and HDL cholesterol levels have been described. We characterized two apo A-I deficiencies and 11 apo A-I structural mutations in which two mutants, apo A-I Oita and apo A-I Nichinan showed low HDL cholesterol levels. These data showed that the central and C terminal domains of apo A-I are involved in this function, leading to low HDL cholesterol levels. However, none of the cases showed a distinct relation of the mutant to coronary artery disease. Further biochemical and clinical evaluations of apo A-I mutation will provide substantial help in understanding the structure-function relationships of apo A-I.

Apolipoprotein A-I↗

[Gastrointestinal bleeding (introduction)].

Gastrointestinal (GI) bleeding is a common and important problem for all clinicians. Patients may present with signs of bleeding, such as hematemesis, melena, or hematochezia. The patient must first be hemodynamically stabilized. Initial assessment of patients with GI bleeding includes thorough history taking and physical examination. Patients with acute bleeding or an unstable condition must be resuscitated immediately and the source of bleeding must be localized to the upper or lower GI tract. Panendoscopy is often the initial diagnostic test and is useful to stop GI bleeding, at the same time.

Emergency Medical Services↗

Antitumor glycogen from scallops and the interrelationship of structure and antitumor activity.

Hot water extract of scallop was treated with actinase E and fractionated by Sephadex G-25 gel-filtration and DEAE Sephadex A-25 ion-exchange chromatography. The antitumor activity of these fractions against Meth-A fibrosarcoma was examined. The nonadsorbed fraction (SCA25A) and weakly adsorbed fraction (SCA25B) obtained on DEAE Sephadex A-25 anion-exchange gel showed strong antitumor activity. Chemical analyses and NMR spectra identified SCA25A and SCA25B as glycogen. However, glycogen extracted from the scallop with trichloroacetic acid and from abalone showed no antitumor activity. This difference was thought to be due to variations in the fine structure of the glycogen molecule. The fine structure of glycogen was investigated by a sequential enzyme digestion method using beta-amylase and pullulanase, while the unit chain was analyzed by high performance anion exchange chromatography. The results showed that the antitumor active glycogen was highly branched with a shorter chain than glycogens without antitumor activity.

Journal Article↗

Anti-streptococcal activity of homologous polymorphonuclear neutrophils from patients with surgically treated oral infections.

The phagocytic bactericidal activity of homologous polymorphonuclear neutrophils (PMN), obtained from patients with severe, moderate and mild oral infections with Streptococci, was investigated. The drop in viable bacterial cell counts in PMNs from 3 patients with a severe infection, after 4 hours of incubation, was much greater than in PMNs from moderate or mild infections. We conclude that the phagocytic bactericidal activity of PMNs is stronger in patients suffering from severe oral infections with Streptococci.

Adult↗

Cloning and characterization of NE-dlg: a novel human homolog of the Drosophila discs large (dlg) tumor suppressor protein interacts with the APC protein.

We have cloned a cDNA for a novel human homolog of the Drosophila discs large (dig) tumor suppressor protein, termed NE-dlg (neuronal and endocrine dig). Northern blot analysis revealed that the gene is highly expressed in neuronal and endocrine tissues. Fluorescence in situ hybridization (FISH) and radiation hybrid mapping studies localized the NE-dlg gene to chromosome Xq13. We also found that the NE-dlg gene encoded a 100 kDa protein. Immunolocalization studies using an NE-dlg antibody showed that the protein tended to be expressed in non-proliferating cells, such as neurons, cells in Langerhans islets of the pancreas, myocytes of the heart muscles, and the prickle and functional layer cells of the esophageal epithelium. Proliferative cells, including various cultured cancer cell lines and basal cells in the esophageal epithelium, showed little expression of the NE-dlg protein. In addition, yeast two-hybrid screening and in vitro binding assays revealed that the NE-dlg interacted with the carboxyl-terminal region of the APC tumor suppressor protein. These data suggest that NE-dlg negatively regulates cell proliferation through its interaction with the APC protein.

Adaptor Proteins, Signal Transducing↗

Disease-free survival for 6 years and 4 months after dissection of recurrent abdominal paraaortic nodes (no. 16) in gastric cancer: report of a case.

We herein report the case of a 63-year-old woman who underwent curative surgery consisting of a subtotal gastrectomy with D2 lymph node dissection for advanced stomach cancer in June 1984, and later underwent systemic dissection of recurrent abdominal paraaortic lymph nodes by a retromesenteric approach in June 1989. Metastatic nodes were found in nos. 16b1 (interaorticocaval), 16b2 (interaorticocaval), and 280 (aortic carinal). One of the resected nodes, which was histologically diagnosed as being poorly differentiated adenocarcinoma, measured approximately 10 x 7 cm and infiltrated the inferior caval vein. There was no distant metastasis except for nodal metastases. Since the reoperation, the patient has been disease-free for 6 years and 4 months, and she continues to visit our hospital as an outpatient. The findings of this case therefore suggest the significance of paraaortic lymph node dissection. To our knowledge, this is the first report in the world of a gastric cancer patient who has remained disease-free for more than 5 years after the systemic dissection of recurrent paraaortic lymph nodes.

Adenocarcinoma↗

Characterization of a cry2A gene cloned from an isolate of Bacillus thuringiensis serovar sotto.

A cry2A-type gene, designated as cry2(SKW), was cloned from Bacillus thuringiensis serovar sotto SKW01-10.2-06, and some unique features of the gene were revealed. The cry2(SKW) gene encoded a polypeptide of 635 residues with a predicted molecular mass of 71,137 Da. Cry2(SKW) had 95.4% identity with Cry2Aa in amino acid sequence and was two residues longer than Cry2Aa. Two open reading frames (ORFs), designated as orf1 and orf2, were present upstream of the cry2(SKW) and showed high homology with the corresponding ORFs in the cry2Aa operon. The Orf2 from SKW01-10.2-06 contained a region of repeated sequences. However, unlike Cry2Aa, Cry2(SKW) formed the cuboidal crystalline inclusions when the cry2(SKW) gene was expressed in an acrystalliferous B. thuringiensis strain in the absence of the upstream ORFs. Furthermore, Cry2(SKW) was less toxic to a lepidopteran species, Bombyx mori, than Cry2Aa in spite of high homology between the two proteins.

Amino Acid Sequence↗

Do reactive oxygen species underlie the mechanism of apoptosis in the tadpole tail?

Although "programmed cell death" has been postulated to underlie the mechanism for the disappearance of the tadpole tail, critical factors that trigger this phenomenon remain to be elucidated. To investigate the mechanism for the disappearance of the tail, changes in morphology, DNA status and the enzymes which metabolize reactive oxygen species were determined in the tail of Rana rugosa tadpoles. Histological examination revealed that apoptotic cell death was apparent in the tail myocytes during metamorphosis. Electrophoretic analysis of the tail DNA revealed a marked fragmentation. During the apoptotic changes, the activity of Cu/Zn-type superoxide dismutase (SOD) in the tail markedly increased with a concomitant decrease in its catalase activity. The apoptotic process was markedly enhanced by adding hydrogen peroxide (H2O2) and aminotriazole, a catalase inhibitor, to the medium. These observations suggested that apoptotic cell death in the tadpole tail might be triggered, at least in part, by a mechanism depending on active oxygen species, such as H2O2.

Amitrole↗

Effects of monatepil, a novel calcium antagonist with alpha 1-adrenergic blocking activity, on the low-density lipoprotein receptor in human skin fibroblasts.

To investigate the mechanisms of the hypolipidemic effect of monatepil, a new class of calcium antagonists with alpha 1-adrenergic blocking activity, we examined the effects of the drug on low-density lipoprotein (LDL) receptor activity and the level of LDL receptor mRNA present in cultured human skin fibroblasts. At concentrations of 2 x 10(-5) M, monatepil increased the binding (248 +/- 43%; mean +/- SD), internalization (374 +/- 18%), and degradation (145 +/- 2%) of 125I-LDL in human skin fibroblasts (n = 3, p < 0.05). Treatment of human skin fibroblasts with 2 x 10(-5) M of monatepil for 6 hours resulted in an increase in LDL receptor mRNA to 163% of the control level (n = 2), as shown by Northern blot analysis. Our results suggest that the hypolipidemic clinical effects of monatepil may be due to increased LDL receptor activity.

Adrenergic alpha-1 Receptor Antagonists↗

Tissue-specific expression of pancreatic-type RNases and RNase inhibitor in humans.

The tissue-specific expression of five human pancreatic-type RNases and RNase inhibitor was analyzed by Northern hybridization against poly(A)+ RNA prepared from 16 normal tissues. The widespread expression of RNase 1 was observed in almost all of the tissues. RNase 4 and angiogenin showed a similar distribution of expression abundantly present in the liver. This suggested the identity of the cell types producing these two molecules. However, no relativity appeared to be present between the vascularization of the tissues and the angiogenin expression. A narrow range of expression of the eosinophil-derived neurotoxin gene was observed. This localization seems related to the phagocytic cells in the tissues. The undetectable level of the eosinophil cationic protein mRNA in normal tissues suggests that the differentiation of eosinophils, triggered by inflammation and/or atopy, is required. The expression of RNase inhibitor was found to be ubiquitous. The regulatory function of inhibitor against RNases in the cell should be considered in studying the physiological significance of the pancreatic-type RNase family.

DNA, Complementary↗

Intramembrane signaling mediated by hydrogen-bonding of water and carboxyl groups in bacteriorhodopsin and rhodopsin.

The light-induced mechanism for proton pumping of bacteriorhodopsin was studied by Fourier transform infrared spectroscopy of the discrete sequential intermediate states, L, M, and N. Attention is focused on L in the early microsecond time range, as a transition state in which the Schiff base forms strong H-bonding with a water molecule coordinated with Asp85. This structure leads to transfer of the Schiff base proton to Asp85 in the L-to-M process, which then triggers proton release from Glu204 to the extracellular surface. H-bonding of Arg82 and water molecules are involved in this process. Chloride can replace Asp85 in the D85T mutant, and this anion will be then transported instead of a proton. In L, structural perturbations are induced also around Asp96, through a string of H-bonding mediated by internal water molecules and peptide carbonyls in helices B and C, and Trp182 in helix F. These may cause the structural changes that occur later in the M-to-N process. Similar interactions, through internal water molecules and the peptide bonds in helices B and C, take place in bovine rhodopsin. They transduce changes across the membrane from the Schiff base to the cytoplasmic surface, where the activation of the transducin occurs.

Animals↗

Cryobacterium psychrophilum gen. nov., sp. nov., nom. rev., comb. nov., an obligately psychrophilic actinomycete to accommodate "Curtobacterium psychrophilum" Inoue and Komagata 1976.

"Curtobacterium psychrophilum," proposed by Inoue and Komagata in 1976, is a psychrophilic gram-positive irregular rod isolated from Antarctic soil. This organism grew optimally at 9 to 12 degrees C and did not grow at higher than 18 degrees C. Chemotaxonomic characteristics of this organism were the presence of 2,4-diaminobutyric acid in the cell wall and menaquinone-10 as the predominant respiratory quinone. The cellular fatty acid profile, which contained a significant amount of an anteiso-branched monounsaturated acid, 12-methyl tetradecenoic acid, was a distinctive characteristic of this organism and was reasonable for adaptation to low temperature. Phylogenetic analysis based on 16S ribosomal DNA sequences revealed that this organism was positioned at a separate branch in the family Microbacteriaceae, actinomycetes with group B peptidoglycan. We propose the name Cryobacterium psychrophilum gen. nov., sp. nov. for this organism. The type strain is JCM 1463 (= IAM 12024 = ATCC 43563 = IFO 15735 = NCIMB 2068).

Actinomycetales↗

Nitric oxide synthase activity in human lung cancer.

Nitric oxide synthases (NOS) exist in human tumor cell lines and solid tumor tissues, and it has been suggested that NO may play important roles in growth, progression or metastasis of tumors. We investigated the activity and distribution of NOS in a series of human cancer and normal lung tissues. Seventy-two primary lung cancer samples (44 cases of adenocarcinoma, 18 of squamous cell carcinoma, 4 of large cell carcinoma, 2 of small cell carcinoma, 2 of adenosquamous carcinoma, and 2 of carcinoids) and corresponding normal lung samples were obtained from surgically treated patients. In normal lung tissues, little NOS activity was observed with no correlation between the patient's age and NOS activity. The total NOS activities in lung adenocarcinoma samples were significantly higher than those in other types of lung cancers of normal lung samples (P < 0.05). Analysis by tumor grade of the adenocarcinoma samples revealed no significant difference of NOS activity between grades. TNM classification showed that, although T stage did not correlate with NOS activity, cancer tissues from patients with N2 disease tended to have lower activity than those from patients with NO or N1 disease. Immunohistochemical studies revealed that the intensity of NOS immunoreactivity correlated with NOS activity. These results suggest that NO may play an important role in the metabolism and behavior of lung cancers, especially adenocarcinoma.

Adult↗

Effect of maternal exercise on fetal umbilical artery waveforms: the comparison of IUGR and AFD fetuses.

OBJECTIVE: To determine the effect of maternal exercise on the fetal blood flow of normal and growth-retarded fetuses. METHODS: The effect of maternal exercise on fetal blood flow was investigated with 24 pregnant women between 36 and 42 weeks' gestation. Seventeen pregnancies were uncomplicated (normal group) and the other 7 were complicated with growth-retarded fetuses (IUGR group). They underwent graded walking on a treadmill with an upper limit of 150 bpm for the maternal heart rate. The systolic over diastolic velocity ratio (S/D ratio) of the umbilical artery was measured before exercise, and at 3, 5, 10, and 15 minutes after exercise. RESULTS: The mean S/D ratio of the IUGR group before exercise was significantly higher than that of the normal group (p < 0.05). The S/D ratio did not change significantly after exercise, in either the normal group or the IUGR group. CONCLUSION: This study suggests that maternal exercise at this level of intensity and duration does not have any harmful effect, even on growth-retarded fetuses that might have placental dysfunctions.

Diastole↗

[Effects of globulin preparations on phagocytic killing of oral streptococci].

The phagocytic bacterial activity on Streptococcus intermedius and Streptococcus oralis, clinical isolates from patients suffering from severe oral surgical infections, was evaluated by using sera and neutrophils of patients who had been treated with polyethylene glycal treated human normal immunoglobulin (Venoglobulin-IH). The phagocytic function of the neutrophils against the two strains, approximately 10 cells/neutrophil, was unrelated to the administration of Venoglobulin-IH. The bactericidal function of the serum and neutrophils on the third day following Venoglobulin-IH administration, on the other hand, rose to 10 times that of the sera and neutrophils of patients with mild infections. The agglutinin titer of Venoglobulin-IH against S. intermedius and S. oralis were 32 and 16 times, respectively, indicating an evident rise in these titers against the clinical isolates in comparison with the reference strains of the same organisms. These findings indicated that the oral streptococci that are isolated from patients with grave infections are associated with an antigenicity that is different from the normal bacterial flora; and these organisms are more labile to phagocytosis by neutrophils that were obtained from patients who have been treated with Venoglobulin-IH.

Administration, Oral↗

Characterization of the inner enamel epithelium in the enamel-free area based on the ability to secrete enamel protein demonstrated by in situ hybridization and immunohistochemistry.

Both the expression of amelogenin mRNA and secretion of amelogenin were investigated in rat molars by in situ hybridization and immunohistochemistry. Probes were designed by multiple-labeling of oligonucleotide probes for in situ hybridization. Amelogenin mRNA first appeared in differentiating ameloblasts of the distal region and some inner enamel epithelial cells of enamel-free area (EFA cells) of the second cusp at postnatal day 0. At the same time, amelogenin protein was detected in the extracellular matrix between dentin and differentiating ameloblasts and in some EFA cells of the second cusp. At postnatal day 1-3, amelogenin was expressed in the secretory ameloblasts, and in the matrix beneath these cells. Both amelogenin mRNA and amelogenin were detected in the EFA cells and their extracellular matrix. After postnatal day 5, amelogenin mRNA and amelogenin were detected in the secretory ameoloblasts and extracellular matrix in the enamel-forming region, respectively. At this time, amelogenin mRNA was not detected in the EFA cells, but a small amount of amelogenin was found in the matrix beneath the EFA cells. These findings suggest that EFA cells differentiate into amelogenin-secreting cells, i.e. ameloblasts, but that the secretion lasts for only a short period at the early stage of tooth development.

Amelogenin↗

Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated with lipoprotein glomerulopathy.

Lipoprotein glomerulopathy (LPG) is a novel disease characterized by proteinuria, lipoprotein thrombi in the glomeruli, and increased concentration of plasma apolipoprotein (apo) E. It is believed that a genetic disorder of apo E may be present and associated with the disease. Three patients with LPG were examined in this study. The patients' DNA sequences were analyzed, and a nucleotide G to C point mutation in exon 4 of the apo E gene was confirmed in each patient. This missense mutation denotes amino acid substitution of the proline residue for arginine residue at position 145 of apo E. This variant (apo E Sendai) may cause a marked molecular conformational change of the apo E. These findings suggest that a novel variant is etiologically related to LPG.

Aged↗

Autoimmune hyperlipidemia with inhibitory monoclonal antibodies against low density lipoprotein binding to fibroblasts in a case with multiple myeloma.

The mechanism of severe hyperlipidemia in a 54-year-old woman with multiple myeloma and monoclonal immunoglobulin A (IgA) gammopathy was investigated. Her plasma total cholesterol and triglyceride concentrations were 29.7 mmol/l (1,150 mg/dl) and 11.9 mmol/l (1,060 mg/dl), respectively. Western blot analysis demonstrated that her low density lipoproteins (LDL) contained IgA. This IgA also was shown to bind to control LDL and inhibited 125I-LDL binding to fibroblasts, suggesting that by binding to the LDL, IgA interfered with LDL binding to LDL receptors. These findings indicate that an inhibitory monoclonal IgA against LDL binding may explain, at least in part, the severe hyperlipidemia observed in this case.

Antibodies, Monoclonal↗