Search PubMed⌕ Search

Biomedical subjects

M Waki

Publications and source records attributed to M Waki.

At least 73 records · Page 4Linked to original sources

Dimeric substance P analogue shows a highly potent activity of the in vivo salivary secretion in the rat.

We have synthesized a dimeric analogue of substance P (SP) COOH-terminal nonapeptide fragment (D-SP-(3-11] and examined the in vivo and in vitro biological activities in the submaxillary gland of the rat. The dimer elicited an enhanced biological response as compared with receptor binding, showing 2.4-fold more potent receptor affinity than its monomer and 75-fold more potent in vivo salivary secretion activity.

Animals↗

[Malignant mesodermal mixed tumor of the bladder: report of a case].

An 81-year-old woman was admitted to our clinic due to gross hematuria. A large bulky pedunculated mass was found in the bladder by cystoscopic examination. Subtotal cystectomy and bilateral cutaneostomy was performed on January 12, 1987. Histologically the tumor was composed of carcinomatous and sarcomatous elements. The carcinomatous element was composed fundamentally of grade 2, transitional cell carcinoma with numerous foci of squamous metaplasia. The sarcomatous element was composed of myxosarcomatous, chondro-sarcomatous pattern and non-differentiated malignant spindle cell component. Immunohistochemical examination demonstrated the presence of cytokeratin and epithelial membrane antigen in the spindle cell and more obvious carcinomatous regions, using the avidin-biotin conjugated immunoperoxidase technique. The patient died 3 months after operation. Autopsy findings showed multiple organ metastasis which were composed of carcinomatous and sarcomatous elements.

Aged↗

[A case of signet ring cell carcinoma of the urinary bladder].

A 67-year-old man was admitted for complaint of gross hematuria on April 9, 1986. Cytoscopic examination was revealed broad-base tumor, its size was thumb's head, at the right lateral wall of the bladder. Ultrasonography and computed tomographic scan of the bladder demonstrated no evidence of invasion to adjacent organs. The biopsy showed signet-ring cell carcinoma. Radiography of the digestive organs showed no abnormality. A partial cystectomy was performed. Histologically the tumor was limited up to submucosa, that is pT1b. The localization of carcinoembryonic antigen (CEA) on tissue of our case, using the peroxidase-antiperoxidase (PAP) method, was evidenced.

Adenocarcinoma, Mucinous↗

The study on cell surface antigens in epithelial tumor of the upper urinary tract: ABH-isoantigen and Thomsen-Friedenreich antigen.

ABH-isoantigen (ABH-Ag) and Thomsen-Friedenreich antigen (T-Ag) were investigated by the Avidin-Biotin-Peroxidase Complex (ABC) method on 47 patients with epithelial tumor of the upper urinary tract (all patients underwent nephroureterectomy including the cuff of the bladder; 30 patients were diagnosed as transitional cell carcinoma of renal pelvis and 17 ureteral organs). The correlations between ABC expression for ABH-Ag and T-Ag with histological grade, stage and prognosis (5 year survival rate) were studied. A correlation was observed between grade (p less than 0.05) and deletion of the antigenicity of ABH-Ag, but no correlation was evident with stage and prognosis. A high correlation was evident, however, between grade (p less than 0.01), stage (p less than 0.01) and prognosis (p less than 0.01) and deletion of the antigenicity of T-Ag. The analysis of ABC expression for ABH-Ag and T-Ag may therefore be valuable for predicting the malignant potential in transitional cell carcinoma of the upper urinary tract. T-Ag determination in particular may provide a useful prognostic probe should it find clinical application.

ABO Blood-Group System↗

[Chronological changes in bacteria isolated from the urinary tract and their drug sensitivities].

Statistical studies were performed on bacterial strains isolated from the urine of patients with various urological disease in our Urological Department between January, 1983 and December, 1987. In 1987, sensitivity tests of antibiotics to various pathogens were carried out. From the outpatients, 5,725 bacterial strains were isolated. S. epidermidis was isolated most frequently (23.8%), followed by Enterococcus species (16.5%), E. coli (14.7%), Streptococcus species (12.6%), Proteus species (5.3%), other GNR (4.6%), P, aeruginosa (4.5%), Klebsiella species (4.4%), and others. From the inpatients, 4,747 bacterial strains were isolated. Enterococcus species was isolated most frequently (23.1%), followed by S. epidermidis (18.7%), Fungi (12.9%), P. aeruginosa (8.0%), other GNR (6.8%), Streptococcus species (5.4%), Enterobacter species (4.8%), E. coli (4.1%), S. aureus (4.1%) and others. Annual change of distribution of organisms indicated that S. aureus from outpatients had a tendency to increase and Streptococcus species had a tendency to decrease. Whereas from inpatients, E. coli, other GNR, Pseudomonas species and Enterobacter species had a tendency to increase, and Streptococcus species, P. aeruginosa, Proteus species and Klebsiella species had a tendency to decrease. S. epidermidis showed a high sensitivity to minocycline and cephalothin, and Enterococcus showed a high sensitivity to ampicillin and minocycline, but did not show good sensitivity to cefoperazone and latamoxef. E. coli showed a high sensitivity to all drug we tested. P. aeruginosa showed a high sensitivity to gentamycin and norflaxacin, but did not show good sensitivity to other many drugs we tested.

Anti-Bacterial Agents↗

Novel feature of metabolism of low density lipoprotein receptor in a mouse macrophage-like cell line, J774.1.

Biosynthesis, processing, and degradation of low density lipoprotein (LDL) receptors were studied in a mouse macrophage-like cell line, J774.1, by immunoprecipitation and immunoblotting with an antibody directed against the COOH-terminal 14 amino acids of the LDL receptor. The molecular weight of the mature LDL receptor of J774.1 cells maintained in RPMI medium was 140,000 under nonreducing condition and 160,000 under reducing condition in sodium dodecyl sulfate-polyacrylamide gels. These sizes are 10,000-15,000 daltons larger than those of the receptor in other mouse fibroblastic cells or P388 leucocyte. However, when J774.1 cells were cultured in Dulbecco's modified Eagle's medium, the molecular weight of the mouse cell lines, 123,000 under nonreducing condition and 153,000 under reducing condition. The larger LDL receptor molecules produced by J774.1 cells cultured in RPMI were insensitive to the treatment with end-alpha-N-acetylgalactosaminidase (O-glycanase), suggesting that aberrant serine/threonine-linked (O-linked) glycosylation might account for the apparent large size. Pulse-chase experiments revealed that the rate of processing of the LDL receptor from precursor to mature form in J774.1 was similar to that in other mouse cell lines, but the rate of degradation was much faster: half-life of the LDL receptor of J774.1 was about 2 h. No significant difference in biological function or lifetime was observed between the normal and the larger LDL receptor. This novel character of molecular size and lifetime of the LDL receptor in J774.1 is discussed in relation to altered maturation and/or modification during receptor biosynthesis.

Animals↗

Dimerization of neurokinin A and B COOH-terminal heptapeptide fragments enhanced the selectivity for tachykinin receptor subtypes.

We have synthesized dimeric analogues of neurokinin A and B COOH-terminal heptapeptide fragments and evaluated their biological activities to contract isolated smooth muscle preparations of the guinea-pig ileum and rat vas deferens. The dimers were fairly active and showed two-fold increased selectivity for receptors in the guinea-pig ileum as compared with monomers. Extremely slow dissociation indicated a possible bivalent interaction between dimer and receptor.

Amino Acid Sequence↗

Insulin modulates early-phase noradrenaline response to glucose ingestion in humans.

To clarify the relationship between the early-phase insulin response and the early-phase noradrenaline (NA) response to glucose ingestion in humans, serum NA, adrenaline, immunoreactive insulin (IRI), C-peptide immunoreactivity, potassium, nonesterified fatty acid and plasma glucose levels were measured in 8 non-diabetics and 10 diabetics without autonomic disturbance after oral 75 g glucose load. Following results were obtained: 1) In non-diabetics, the maximal NA response was observed at 30 min after glucose ingestion, but in diabetics, mean serum NA levels remained unchanged. The effect of glucose ingestion on the NA response was significantly different between non-diabetics and diabetics by the repeated measurements analysis of variance (F ratio = 5.72, P less than 0.05). 2) In total group (n = 18), at early-phase after glucose ingestion (at 30 min), positive correlation was found between dIRI level and dNA level (r = 0.52, P less than 0.05), between dIRI level and %dNA level (r = 0.56, P less than 0.05), between dIRI/dglucose ratio (insulinogenic index) and dNA level (r = 0.70, P less than 0.01). 3) In four diabetics, NA responses to glucose ingestion were studied again after mild energy restriction for 2 wk. In three of them, both early-phase IRI response and early-phase NA response to glucose ingestion improved after diet therapy, but in the remainder, early-phase NA response to glucose ingestion remained unchanged in accordance with sustained impaired early-phase insulin response to glucose ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Exercise-induced increase in glandular kallikrein activity in human plasma and its significance in peripheral glucose metabolism.

Glucose uptake into skeletal muscle of human forearm at rest and during exercise is reported to be diminished by the administration of a kallikrein (kallidinogenase) inhibitor. The present study was conducted to clarify the changes of glandular kallikrein (GK) activity in human plasma during acute exercise and its significance in peripheral glucose metabolism. 10 non-diabetic inpatients, aged 49.5 years, and 8 diabetic inpatients, aged 53.8 years, were studied. After an overnight fast, bicycle ergometer exercise test was performed for 15 min (25 W (5 min)----50 W (5 min)----75 W (5 min]. Before (basal), during (at 15 min) and after exercise (at 25 min), venous blood samples were drawn to determine plasma GK activity and glucose, serum immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), nonesterified fatty acids, pyruvate, lactate, noradrenaline and adrenaline levels. In the 1st trial, in both non-diabetics (n = 10) and diabetics (n = 8), plasma GK activity increased significantly during exercise. After the 1st trial, in 6 patients (5 non-diabetics; 1 diabetic), exercise test was repeated once after 2-4 weeks and in a diabetic patient, exercise test was repeated twice at 4-week intervals, accordingly exercise test was performed 26 times in 18 patients in total. Natural logarithmic correlation between sigma glucose level and sigma GK activity (r = 0.52, n = 26), and hyperbolic correlation between sigma glucose level and sigma IRI level (r = -0.66, n = 26) but no correlation between sigma glucose level and sigma CPR level (r = 0.17, n = 26) were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

[A pathological study of relatively early stage cancers of the gallbladder, and the significance of the full thickness cholecystectomy].

The mode of extension of relatively early-stage gallbladder cancer(ss) was studied by microscopic serial sections in 25 patients. We also investigated the detached surface of the liver bed and gallbladder wall. No intrahepatic infiltration was noted in ss cancer and no recurrence occurred in the liver bed surface when a full-thickness resection was performed. The ss cancers in the fundus and in the body were found to extend subserously in the direction of the cervix or circumferentially. The infiltration reached the surrounding area of the common hepatic duct in 3 cases. Mucosal expansion showed the same directional tendency, but usually did not reach the cystic duct. On the other hand, the ss cancers of the cervix and the cystic duct frequently showed subserosal extension into the periductal interstitial tissue in the hepatoduodenal ligament. These results suggest that recurrence of ss cancers of the fundus and body after simple cholecystectomy might be partially caused by incomplete resection of the liver bed portion of the gallbladder wall, and a full-thickness cholecystectomy for cholecystolithiasis was considered to be useful to decrease the risk of recurrence of occult gallbladder carcinoma.

Cholecystectomy↗

[Study of the Thomsen-Friedenreich antigen in bladder tumors].

Thomsen Friedenreich antigen (T-ag), ABH isoantigen (ABH-ag) in 106 cases with bladder tumor (all transitional cell carcinoma) of various histological grades and stages were investigated by the Avidin-Biotin-Peroxidase Complex (ABC) method. There was a correlation between histological grade, stage and deletion of the antigenicity (T-ag and ABH-ag). In a follow-up study of 45 patients with low grade and low stage tumor, the recurrence rate after surgery of the cases with abnormal antigenicity (T-ag and ABH-ag) was significantly higher than that of the cases with the normal antigenicity. Combination of two markers (T-ag and ABH-ag) was significantly more effective than the single marker.

ABO Blood-Group System↗

Anti-chymotrypsin and anti-elastase activities of a synthetic bicyclic fragment containing a chymotrypsin-reactive site of soybean Bowman-Birk inhibitor.

A bicyclic hexadecapeptide, which corresponds to the sequence 36-51 and contains the chymotrypsin-reactive Leu-43-Ser-44 bond of soybean Bowman-Birk inhibitor, has been synthesized. This peptide consists of two loops formed by disulfide bridges between Cys-36 and Cys-51 and between Cys-41 and Cys-49. The bicyclic peptide showed a strong anti-chymotryptic activity with a Ki of 7.1.10(-7) M. Comparison of inhibitory activity and digestive stability against chymotrypsin with other hexadecapeptides having the same sequence but lacking one or both disulfide bridges suggested that the compact bicyclic structure increases the activity and protects the Leu-Ser bond from chymotryptic digestion. Interestingly, the bicyclic peptide was found to inhibit porcine pancreatic elastase with a Ki of 4.3.10(-5) M, indicating the broad specificity of this ring system.

Amino Acid Sequence↗

Altered function and structure of low-density lipoprotein receptor in compactin (ML236B)-resistant mutants of Chinese hamster cells.

Mutants resistant to compactin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, have been previously isolated from the Chinese hamster V79 cell line. Two compactin-resistant mutants, MF-1 and MF-2, show altered responses to human low-density lipoprotein (LDL). Accumulation of fluorescent-labeled LDL was much reduced. Ligand blotting showed LDL receptor activity in MF-1 and MF-2 cells of about one half to one third that of V79. Internalization and degradation of LDL in MF-1 or MF-2 cells were about one tenth those in V79 cells, suggesting that the LDL binding as well as the LDL internalization of the compactin-resistant clones was altered. Down-regulation of LDL receptor activity as well as hydroxymethylglutaryl CoA reductase was observed in V79 cells treated with LDL, while there appeared to be much less down-regulation in MF-1 and MF-2 cells. Using anti-LDL receptor antibody, MF-1 and MF-2 cells were found to produce smaller-sized mature forms of LDL receptor: the molecular mass of the mutant LDL receptor was 3-5 kDa smaller than that of the parental LDL receptor. Altered O-linked oligosaccharides or amino acid sequence might account for the decreased molecular mass and aberrant properties of the LDL receptor in MF-1 and MF-2.

Animals↗

[4,4'-(Z)-dehydrophenylalanine]gramicidin S with stabilized bioactive conformation and strong antimicrobial activity.

Dehydrophenylalanine (delta Phe) was incorporated into an antibiotic peptide gramicidin S (GS) in place of D-Phe4,4' to prepare an unsaturated analog. Conformational analysis with 1H-NMR indicated that the unsaturated analog has much the same backbone conformation as that of natural gramicidin S as shown by NOE experiments. Studies on temperature dependences and on the chemical shift differences showed that the hydrogen bonds between Val-NH and Leu-CO in the unsaturated analog are strengthened by the incorporation of delta Phe4,4'. This resulted in the reinforcement of the beta-sheet structure which is the most important structural element for GS bioactivity. [delta Phe4,4']gramicidin S exhibited indeed very strong antimicrobial activities against Gram-positive bacteria as well as the natural peptide.

Circular Dichroism↗

Low binding capacity and altered O-linked glycosylation of low density lipoprotein receptor in a monensin-resistant mutant of Chinese hamster ovary cells.

We have studied function and structure of the low density lipoprotein (LDL) receptors in a monensin-resistant (Monr-31) mutant isolated from Chinese hamster ovary (CHO) cells. To assay the ability of the receptor to bind LDL, we employed three methods, 125I-LDL binding to the cells at 4 degrees C, 125I-LDL binding to the receptor-phospholipid complex (Schneider, W.J., Goldstein, J.L., and Brown, M.S. (1980) J. Biol. Chem. 255, 11442-11447), and ligand blotting (Daniel, T.O., Schneider, W.J., Goldstein, J.L., and Brown, M.S. (1983) J. Biol. Chem. 258, 4606-4611). The LDL receptor number was similar in both CHO and Monr-31, but the binding affinity was reduced in the mutant. The semi-quantitative immunoblotting assay with an antibody directed against the COOH-terminal 14 amino acids and the ligand-blotting assay with LDL also showed that the relative steady-state level of the receptor in Monr-31 was comparable to that in CHO, whereas the binding capacity of the receptor in Monr-31 was lower than that in CHO. The precursor and degradation forms of the LDL receptors produced in the mutant cells were similar in size to those in the parental cells, but the apparent molecular mass of the mature receptor protein in sodium dodecyl sulfate-polyacrylamide gels was reduced about 5000 daltons in the mutant. These results suggest a structural change at the NH2-terminal LDL binding domain. Tests of the effects of tunicamycin, endo-alpha-N-acetylgalactosaminidase (O-glycanase), and sialidase (neuraminidase) on the molecular size of the mature receptors indicated that the reduced size of the receptor in the mutant cells resulted from altered oligosaccharide chain(s) linked to serine/threonine residues in the binding domain. We compared the molecular sizes and binding activity of human LDL receptors in several clones derived from CHO and Monr-31 cells which were transfected with human LDL receptor cDNA. The human LDL receptors produced in the transfected clones of Monr-31 were also smaller in molecular size and lower in binding capacity than those produced in the transfected clones of CHO. These results suggest that both structural and functional alteration of the LDL receptor of Monr-31 is not caused by a mutation in the structural gene of the LDL receptor but by altered processing or maturation of the receptor. The correlation of the decrease in molecular size and reduced binding capacity of the LDL receptor is discussed.

Animals↗

Environment-dependent conformation and antimicrobial activity of a gramicidin S analog containing leucine and lysine residues.

An analog of gramicidin S, cyclo(-L-Leu-L-Lys-L-Leu-D-Leu-L-Leu-)2, in which four out of five amino acid components of gramicidin S were substituted, has been synthesized. This analog assumes a conformation similar to that of gramicidin S in acidic liposomes and a random conformation in neutral liposomes. The antimicrobial activity of this analog corresponded to one-fourth of that of gramicidin S. A possible mechanism for conformational changes in acidic liposomes is discussed.

Amino Acid Sequence↗