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Biomedical subjects

M Waki

Publications and source records attributed to M Waki.

At least 91 records · Page 5Linked to original sources

Interaction of dimers of inactive enkephalin fragments with mu opiate receptors.

Dimeric analogues of the inactive enkephalin fragment Tyr-D-Ala-Gly were synthesized by cross-linking with alkanediamine at the C-terminus. Biological evaluation of these dimers (H-Tyr-D-Ala-Gly-NH)2.(-CH2-)n (DTREn), where n = 0-6, revealed that the fragment inactive for mu receptors was activated by its dimerization, with the maximum activation found with DTRE2, and that the dimer was highly mu-selective. So-called "handicapped" dimers, which lack one of the essential groupings required for enkephalin activity, were found to be far less active, indicating that the dimer interacts bivalently with mu receptors. It seems, therefore, that mu opiate receptors contain at least two equivalent binding sites which are extremely close to each other.

Animals↗

Relationship between protein intake and nitrogen balance in obese patients on low energy diet.

The effect of nitrogen intake on nitrogen balance was studied in six obese patients receiving low energy diets. They were given a control diet containing 2,000 kcal of energy and 80 g of protein for the first ten days. Then they were given Diet A with 1,100 kcal of energy and 70 g of protein for the next 2 weeks, followed by Diet B with 1,100 kcal of energy and 50 g of protein for 2 weeks. The relationship between nitrogen intake (X, mg/kg) and nitrogen balance (Y, mg/kg) during the low energy diet periods was statistically significant, with Y = 0.388X-60.32 (SD = 17.71, r = +0.67, n = 11, p less than 0.05). The nitrogen and protein requirements were estimated from this equation to be 201.1 mg/kg and 1.26 g/kg, respectively. In our experiment, the nitrogen balance in obese patients was well maintained although total energy was reduced to 1,100 kcal/day in Diet A. It is suggested that protein quantity in the diets should be taken into account when a low energy diet is used for the treatment of obesity.

Blood Proteins↗

Effects of low energy diets on protein metabolism studies with [15N]glycine in obese patients.

The effects of low energy diets on protein metabolism in terms of the metabolic pool, active protein pool, and active and inactive protein synthesis rates were studied using [15N]glycine in five obese patients (percentage of ideal body weight, 120-190%). For 10 days, the patients were given a control diet containing 2,000 kcal of energy and 80 g of protein. For the next 2 weeks, they were given Diet A with 1,100 kcal of energy and 70 g of protein, and for the last 2 weeks given Diet B with 1,100 kcal of energy and 50 g of protein. During the Diet A period, the active protein pool and the active and inactive protein synthesis rates were about the same as during the control diet period, although the metabolic pool tended to be slightly smaller than during the control diet period. During the Diet B period, the metabolic pool, active protein pool, and active protein synthesis rate were all significantly different from the values during the control diet period. The results suggest that protein metabolism in obese patients is not maintained with less than 70 g of protein daily when energy intake was restricted to 1,100 kcal/day.

Body Weight↗

[The study of the ABH isoantigen of bladder tumors].

ABH isoantigens in 82 cases with bladder tumor of various grades and stages were investigated by the avidin-biotin-peroxidase complex (ABC) method. Correlation of ABC expression for isoantigens with pathological findings on the grading and staging system of the bladder tumors were as follow: Of 60 cases of low grade tumors, 34 (56.7%) were positive and of 22 cases of high grade tumors, 21 (95.5%) were negative. Of 63 cases of low stage tumors, 35 (55.6%) were positive and all 19 cases of high stage tumors, (100%) were negative. The isoantigens in the tissue of the bladder tumors tended to disappear as the histologic anaplasia of the tumor progressed. There was a high correlation between the histological grade, stage and ABC expression (p less than 0.01). In a follow-up study of 38 patients with low grade, low stage, initial transitional cell carcinoma, 9 of the 24 patients positive for ABC expression (37.5%) showed recurrence during the 1 to 6 year follow-up period, whereas 10 of the 14 patients negative for ABC expression 10 (71.4%) did. There was a high correlation between the recurrence rate and ABC expression (p less than 0.05). Therefore, the analysis in the bladder tumors may be valuable for prediction of malignant potential, especially for the low grade, low stage tumors.

ABO Blood-Group System↗

[Study on heterotransplantation of human malignant urogenital tumors in nude mice: establishment of the tumor line in nude mice from human primary ureteral tumor and its characteristics].

The tumor line in nude mice is one of the most important experimental animal models for oncodevelopmental studies. We implanted a human ureteral tumor into nude mice, established the tumor line, AM-UT-1, and maintained it by serial transplantation. The characteristics of this tumor line in nude mice are reported. Histologically, the original tumor was a transitional cell carcinoma (grade II, stage B). The transplanted tumor grew locally and had a constant growth pattern during serial passage until the 13th passage in nude recipients and maintained the basic histological, immunohistochemical findings of the original tumor. Both original tumor and serial transplanted tumor had carcinoembryonic antigen (CEA)-producing activity. A high level of serum CEA was also recognized in nude mice.

Animals↗

Cyclic peptides. XXVI. Synthesis of AM-toxin II analogs by cyclization through ester bond formation.

In order to explore the route for the preparation of cyclodepsipeptide by cyclization through an ester bond formation, two analogs of AM-toxin II, cyclotetradepsipeptide, were synthesized. As a preliminary experiment, synthesis of [L-Phe3, L-Ser(Bzl)4]-AM-toxin II, containing L-Phe and L-Ser(Bzl) in place of L-App (2-amino-5-phenyl-pentanoic acid) and delta Ala (alpha, beta-dehydroalanine), respectively, was attempted. Cyclization of H-L-Hmb-L-Phe-L-Ser(Bzl)-L-Ala-OH in CH2Cl2 at 10 mM concentration using water-soluble carbodiimide (EDC) and 4-dimethylaminopyridine (DMAP) successfully gave a cyclic monomer in 16% yield. Cyclization of H-L-Hmb-L-App-L-Ser(Bzl)-L-Ala-OH under the same conditions also afforded a cyclic monomer, [L-Ser(Bzl)4]AM-toxin II, in 19% yield. Analytical parameters of these cyclic monomers obtained were identical to those of the authentic samples obtained by cyclization through a peptide bond formation.

Indicators and Reagents↗

Preparation of tyrosine-O-[35S]sulfated cholecystokinin octapeptide from a nonsulfated precursor peptide.

A rapid and simple one-pot method for O-sulfation of nonsulfated cholecystokinin octapeptide (CCK-8) was developed using sulfuric acid and dicyclohexylcarbodiimide (DCC) without protection of the amino acid side chains. The extent of sulfation was increased with increasing the amount of reactants, sulfuric acid, and DCC, and reached maximum (40%) with fourfold molar excess of sulfuric acid and 40-fold molar excess of DCC. The excess of nonsulfated peptide inhibited the sulfation. The sulfation product was purified by HPLC or TLC to give a pure sulfated substance which showed exactly the same behavior as that of an authentic O-sulfated CCK-8 on HPLC or TLC. The purified sulfated peptide was active in stimulating amylase secretion from rat pancreatic fragments, and amino acid analysis showed that the tyrosine residue in the peptide existed in O-sulfated form. Sulfation with [35S]sulfuric acid-DCC produced a radioactive substance, from which O-[35S]sulfated CCK-8 could be easily purified by two-dimensional TLC.

Cholecystokinin↗

Opiate receptor binding characteristics of dimeric analogues of mu-selective DAGO-enkephalin.

DAGO-enkephalin ([ D-Ala2, MePhe4, Gly-ol5]enkephalin), a highly selective ligand for mu opiate receptors, was dimerized with a series of alpha,omega-alkanedioic acids (n = 2-12) at the OH-terminus. In the radioligand receptor binding assays with rat brain, most of the DAGO-enkephalin dimers with cross-linking methylene chain n (DEDn) were more potent than DAGO monomer. For delta receptors, affinity of DEDn was maximized with n = 8, which might be related to an optimal distance between two binding sites. For mu receptors, an increase in chain length resulted in a progressive loss of potency. Although all of DEDn are considerably mu-selective, with a mu/delta ratio of 15-50, DEDn exhibited fairly flat binding curves with 15-50% smaller sloped than that of DAGO, suggesting that the dimers interact more strongly with one of the possible two mu binding sites.

Animals↗

[Clinical experience with T-2588 in complicated urinary tract infections].

The clinical effectiveness and safety of T-2588 were evaluated in 21 patients with complicated urinary tract infections. Six hundred mg of T-2588 per day was administered orally in three divided doses for 14 days. The results were excellent in 7 cases (33.3%), moderate in 8 cases (38.1%) and poor in 6 cases (28.6%), and the effectiveness rate was 71.4%. The effectiveness rates of the single infection group and mixed infection group were 91.7% and 44.4%, respectively. The overall bacteriological eradication rate obtained was 77.1%, and those of gram-positive cocci and gram-negative rods were 62.5% and 81.5%, respectively. None of the 21 cases, had any significant side effects and abnormal laboratory findings. From the above results, T-2588 is considered to be a useful antibiotic in the treatment of complicated urinary tract infections.

Adult↗

[A clinical study on testicular tumor].

The 19 cases of testicular tumors treated at our Hospital between 1974 and 1983, were reviewed retrospectively. The incidence of testicular tumors among the male outpatients in our urologic clinic was 0.31%. The patients ranged in age from 1 to 76 years old (average: 27.8 years old). The affected side was the left side in 11 and the right side in 8 cases. The most frequent symptom was a painless mass of the testis. Histopathological diagnosis according to the classification by Dixon and Moore was type I in 9 cases, type II in 4 cases, type II in 1 case, type IV in 4 cases. Thus germinal tumors accounted for 18 (94.7%) of the cases. One case (5.3%) of malignant lymphoma was non-germinal. As for the age distribution, two peaks were noted in testicular tumors, especially in cases with potential embryonal carcinoma, between 1 and 2 years and between 19 and 32 years. On the other hand, the cases with potential seminoma showed one peak between 25 and 44 years. The treatment consisted of high orchiectomy alone, orchiectomy with radiation, orchiectomy with chemotherapy or orchiectomy with radiation and chemotherapy. Retroperitoneal lymphadenectomy was not done in any case. The over-all 3-year and 5-year actual survival rates were both 92%.

Adolescent↗

[A study on the levels of cefoperazone in urological organs].

The concentration of Cefoperazone (CPZ) in urological organs and serum was measured after the intravenous administration of 2 g of CPZ. Serum levels on healthy adults attained a maximal value of 122.1 +/- 4.2 micrograms/ml at 30 minutes. Serum levels of patients operated under general anesthesia attained a maximal value of 159.0 +/- 13.9 micrograms/ml at 30 minutes. Serum concentration on operated cases continued to be 1.3-2.2 fold higher than that of the healthy adults. Prostate tissue levels attained a maximal value of 80.9 +/- 3.6 micrograms/g at 30 minutes, vesical tissue levels were 52.1 +/- 1.3 microgram/g at 60 minutes and renal tissue were 94.0 +/- 14.5 micrograms/g at 90 minutes. Judging from the minimal inhibitory concentration of CPZ, CPZ seemed to be clinically useful in the treatment of urological infections.

Adult↗

[A case of solid and cystic acinar cell tumor of the pancreas].

A 35-year-old woman with a tumor of the pancreatic head is presented. A filling defect, suggesting an extragastric mass, was found in the photofluorogram of a gastric mass survey. But she had no complaints. CT showed a cystic mass in the pancreatic head, but ERCP and celiac angiography indicated no invasive findings. The resected tumor, wrapped well with a partially calcifying fibrous capsule, measured 7 X 7 X 5 cm and was mostly necrotic. On histological examination, malignant findings, were not revealed. PAS-positive granules and zymogen-like granules were found in the cytoplasm by electronmicroscopic examination. Immunohistochemically, alpha 1-antitrypsin granules were detected.

Adult↗

[clinical studies on primary renal pelvic tumors].

The 15 cases of the primary renal pelvic tumors treated at our Hospital between 1974 and 1983, were reviewed retrospectively. The patients ranged in age from 41 to 74 years old (average: 58.3 years old). There were 11 males and 4 females, the ratio being 2.8:1.0. The affected side was left in 9 cases and right in 6 cases. The most frequent symptom was macrohematuria, which was seen in 12 cases (80%). The major finding of IVP was non-functioning kidney, which was seen in 8 cases (53.3%). Positive urinary cytology was obtained in 8 cases (53.3%). As the surgical method, total nephroureterectomy with bladder cuff was performed in 8 cases, nephroureterectomy in one case and nephrectomy in 6 cases. Histologically, 14 cases were transitional cell carcinoma and one case was squamous cell carcinoma. Simultaneous urothelial tumors were seen in the bladder of 2 patients. A subsequent ureteral tumor was found in one of the 7 cases in which ureters were resected incompletely, and subsequent bladder tumors were found in 8 of the 15 cases receiving surgical treatment in the follow-up period. All of tumors were found within 2 years after operation. Over-all actual survival rates at 1, 3 and 5 years were 87%, 67%, 48%, respectively. Three and 5 year actual survival rates were 100%, 100% respectively for the low stage group and 59%, 29% respectively for the high stage group. Three and 5 year actual survival rates were 100%, 78%, respectively for the low grade group and 44%, 27% respectively for the high grade group. Among several factors, stage and grade of the tumor were the most influencing factors for prognosis.

Adult↗

[Clinical studies on primary ureteral tumors].

The 15 cases of the primary ureteral tumors treated at our Hospital between 1974 and 1983, were reviewed retrospectively. The incidence of primary ureteral tumors among the outpatients in our urologic clinic was 0.15%. The patients ranged in age from 50 to 75 years old (average: 65.5 years old). There were 11 males and 4 females, the ratio being 2.8:1.0. The right ureter and the lower third of the ureter were involved more frequently than other areas. The most frequent symptom was macrohematuria which was seen in 12 cases (80%). The major finding of IVP was non-functioning kidney, which was seen in 11 cases (73.3). Positive urinary cytology was obtained in 9 cases (60%). Twelve patients underwent nephroureterectomy with bladder cuff or total cystectomy. Histologically, all cases were transitional cell carcinoma. Simultaneous urothelial tumors were seen in the bladder in 4 cases (26.7%). The over-all actual survival rates at 1, 3 and 5 years were 59%, 42%, 42%, respectively. The 5-year actual survival rate was 63% for the low grade group and 0% for the high grade group. The 5-year actual survival rate was 82% for the low stage group and 0% for the high stage group. Among several factors, grade and stage of the tumor were the most influencing factors for prognosis.

Aged↗

Cyclic peptides. XVI. Syntheses of AM-toxin I analogs containing a lower or higher homolog of the component L-2-amino-5-(p-methoxyphenyl)pentanoic acid residue.

In order to investigate the influence of the side-chain length at position 3 of AM-toxin I (cyclic tetradepsipeptide) on necrotic activity for apple leaf, two analogs of AM-toxin I, [L-2-amino-4-(p-methoxyphenyl)butanoic acid]-AM-toxin I and [L-2-amino-6-(p-methoxyphenyl)hexanoic acid]-AM-toxin I, were synthesized by the conventional method. Spectra of 1H-n.m.r., u.v. and CD of the analogs were similar to those of natural or synthetic AM-toxin I. The toxic activities of the analogs for apple leaf, however, were weak, indicating that the exact side-chain length at position 3 must be one of the important factors for the induction of the activity. The interaction between AM-toxin I and a possible receptor on apple leaf is discussed.

Circular Dichroism↗

[4,4'-D-diaminopropionic acid]gramicidin S: a synthetic gramicidin S analog with antimicrobial activity against Gram-negative bacteria.

Gramicidin S is especially active against Gram-positive bacteria; e.g., Staphylococcus aureus. An analog, [4,4'-D-diaminopropionic acid]gramicidin S, which contains D-diaminopropionic acid residues instead of D-phenylalanine residues, has been synthesized. This analog is active against some of the Gram-negative bacteria; e.g., Escherichia coli and Salmonella typhosa. Activities of several related analogs are discussed.

Bacteria↗