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Biomedical subjects

M Shimamura

Publications and source records attributed to M Shimamura.

At least 127 records · Page 7Linked to original sources

Angiotensin III: a potent inhibitor of enkephalin-degrading enzymes and an analgesic agent.

Various angiotensins, bradykinins, and related peptides were examined for their inhibitory activity against several enkephalin-degrading enzymes, including an aminopeptidase and a dipeptidyl aminopeptidase, purified from a membrane-bound fraction of monkey brain, and an endopeptidase, purified from the rabbit kidney membrane fraction. Angiotensin derivatives having a basic or neutral amino acid at the N-terminus showed strong inhibition of the aminopeptidase. Dipeptidyl aminopeptidase was inhibited by angiotensins II and III and their derivatives, whereas the endopeptidase was inhibited by angiotensin I and its derivatives. The most potent inhibitor of aminopeptidase and dipeptidyl aminopeptidase was angiotensin III, which completely inhibited the degradation of enkephalin by enzymes in monkey brain or human CSF. The Ki values for angiotensin III against aminopeptidase, dipeptidyl aminopeptidase, endopeptidase, and angiotensin-converting enzyme, which degraded enkephalin, were 0.66 X 10(-6), 1.03 X 10(-6), 2.3 X 10(-4), and 1.65 X 10(-6) M, respectively. Angiotensin III potentiated the analgesic activity of Met-enkephalin after intracerebroventricular coadministration to mice in the hot plate test. Angiotensin III itself also displayed analgesic activity in that test. These actions were blocked by the specific opiate antagonist naloxone.

Acetylcholinesterase↗

[Wilms' tumor in an adult patient: a case report].

A case of Wilms' tumor in an adult patient is presented. The tumor in adults is rather rare and has an unfavorable prognosis. A 39-year-old man bruised his left flank while skiing in February, 1983. He noticed severe left flank pain. The pain subsided after a week of rest. However, he complained of left abdominal mass and dull pain again, and consulted our outpatient clinic on May 21, 1983. Left transperitoneal nephrectomy was performed under a diagnosis of left injured renal tumor. Histological diagnosis was nephroblastoma. A combined chemotherapy of actinomycin D (ACD) and vincristine (VCR) was started after operation. A total of 10 mg of ACD and 14 mg of VCR was administered by the end of 1983. In March 1984, however, a local recurrence and pulmonary metastases of the tumor were detected by CT and chest films. Local RF-hyperthermia combined with irradiation, alpha-interferon or chemotherapy using cisplatin and adriamycin was given. The patient died of profound cachexia in December, 1984 after gradual deterioration of general conditions.

Adult↗

[Bilateral ureteral tumors associated with chronic renal failure: a case report].

A 66-year-old female with bilateral ureteral tumors associated with chronic renal failure is presented. She received pan-hysterectomy due to uterine cancer in 1957. She was first referred to our clinic to make internal shunt under a diagnosis of chronic renal failure. In 1979, the diagnosis of neurogenic bladder and bilateral vesicoureteral reflux (rt; grade 3, lt; grade 1) was made. She was admitted to our clinic with complaints of macroscopic hematuria and a temperature of 39 degrees C on April 28, 1983. Cystoscopically, pyuria from the right ureteral orifice was found. Right retrograde pyelography revealed severe dilatation of the right ureter and renal pelvis with some filling defects. For drainage of pus retaining in the right renal pelvis, right percutaneous nephrostomy was made under the guidance of ultrasonography. After her general condition improved, right nephroureterectomy was performed under the diagnosis of right pyonephrosis on June 8, 1983. Right pyelonephritis and right ureteral tumor, grade 3, were pathologically demonstrated. After the operation, an invasive bladder tumor was detected on cystoscopy and ultrasonography, subsequently a total of 3,900 rad irradiation was given to the bladder tumor. She died of pulmonary edema 7 months later. Autopsy demonstrated a transitional carcinoma, grade 3, of the left ureter. Bilateral urothelial tumors of the upper urinary tract is rare, and to our knowledge only 29 cases have been reported in Japan.

Aged↗

[A new treatment of simple renal cyst: percutaneous instillation of minocycline hydrochloride into simple renal cyst].

Minocycline hydrochloride was percutaneously instilled into simple renal cysts to prevent recurrence of renal cysts after the puncture and aspiration of cystic fluid. Fifty-six simple renal cysts in 51 patients were punctured with an 18-gauge needle under ultrasonographic guidance, and the cystic fluid was aspirated under fluoroscopic control. A single 100 mg or 200 mg dose of minocycline hydrochloride dissolved in 5 ml of distilled water was instilled through the needle into the renal cyst. The patients were followed up by computed tomographic (CT) scan and ultrasonography 1, 3, 6 and 12 months after the treatment. Efficacy was evaluated after 3 months or longer. Of 20 renal cysts instilled with 100 mg of minocycline, efficacy was excellent in 10, good in 6 and poor in 4. Of 22 renal cysts instilled with 200 mg of minocycline, efficacy was excellent in 10, good in 9 and poor in 3. No significant difference was noted between the efficacy rate of 100 mg and 200 mg treatments. Complications attributable to treatment were observed in 15 patients: moderate pain in one, slight pain in 6, slight fever in 8 and slight hematuria in one. Neither severe adverse reactions nor infections were observed in any of the patients. These results suggest that the percutaneous instillation of minocycline into simple renal cysts is a new, simple, safe and effective treatment to prevent recurrence of the cyst and additionally to prevent infection following the puncture.

Administration, Cutaneous↗

Effect of human recombinant granulocyte colony-stimulating factor on hematopoietic injury in mice induced by 5-fluorouracil.

Intravenous (IV) administration of 5-fluorouracil (5-FU) caused severe hematopoietic injury in mice. Daily administration of purified human recombinant granulocyte colony-stimulating factor (rG-CSF) accelerated recovery from neutropenia in these injured mice. Granulocyte-macrophage progenitors (CFU-GM) in spleen were markedly increased by rG-CSF, while rG-CSF was less effective on the regeneration of CFU-GM in femoral marrow. The accelerated recovery from neutropenia in the mice might be mainly due to the stimulation of granulopoiesis in spleen by rG-CSF.

Animals↗

[Detection of beta-lactamase-producing bacteria from female patients with acute uncomplicated cystitis].

A total of 122 bacterial strains isolated from urine specimens of 113 female patients with acute uncomplicated cystitis were used for the study of beta-lactamase production and their susceptibility to various antimicrobial agents was determined. Beta-Lactamase activity was qualitatively determined by a paper strip acidimetric method with benzylpenicillin as substrate and by chromogenic cephalosporin methods using pyridine-2-azo-p-dimethylaniline cephalosporin or nitrocefin as substrate. Susceptibility to antimicrobial agents, including ampicillin, carbenicillin, cephalexin, cephalothin, gentamicin, minocycline, fosfomycin, pipemidic acid and sulfamethoxazole-trimethoprim was examined by a disc method. The beta-lactamase-producing strains detected by at least one of the three tests were found in 18 of 105 Escherichia coli isolates and in the single strain of Enterobacter cloacae dermidis, 3 Enterococcus faecalis and 1 Staphylococcus aureus produced beta-lactamase. The isolation rate of strains resistant to ampicillin, carbenicillin and cephalothin in the beta-lactamase-producing strains was significantly higher than that in the non-beta-lactamase-producing strains (p less than 0.01). These results suggest that beta-lactamase plays an important role in developing resistance to beta-lactam antibiotics in patients with uncomplicated urinary tract infection as well as complicated infection.

Acute Disease↗

Sensitive determination of deuterated and non-deuterated tryptophan, tryptamine and serotonin by combined capillary gas chromatography and negative ion chemical ionization mass spectrometry.

Sensitive methods for the determination of deuterated and non-deuterated tryptophan, tryptamine and serotonin by combined capillary gas chromatography and negative ion chemical ionization mass spectrometry were developed. [3,3-2H2]-L-Tryptophan, which was used as a tracer, was synthesized for studies of their in vivo metabolism. Tryptophan was converted into its trifluoroacetylmethyl derivative after prepurification with an AG 50W-X2 cation-exchange column. Tryptamine and serotonin were extracted with 20% butanol in diethyl ether and derivatized with trifluoroacetic anhydride. These derivatives were separated and determined by selected ion monitoring. In these determinations, [2',3,3,4',5',6',7'-2H7]-D,L-tryptophan, [alpha,alpha,beta,beta-2H4]tryptamine and [alpha,alpha,beta,beta-2H4]serotonin were used as internal standards.

Chemical Phenomena↗

Sensitive determination of tyrosine metabolites, p-hydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenyl-acetic acid and 4-hydroxy-3-methoxymandelic acid, by gas chromatography-negative-ion chemical-ionization mass spectrometry. Application to a stable isotope-labelled tracer experiment to investigate their metabolism in man.

A method has been established for studying the dynamic metabolism of tyrosine to its metabolites in humans using a deuterium-labelled amino acid. Phenylalanine-d5 was administered orally to human subjects (5 mg/kg) and the levels of p-hydroxyphenylacetic acid-d4, 4-hydroxy-3-methoxyphenylacetic acid-d3, and 4-hydroxy-3-methoxymandelic acid-d3 excreted into urine every hour were determined by gas chromatography-negative-ion chemical-ionization mass spectrometry. This method was also applied to some patients with depression and it was possible to detect a slight alteration in the excretion of some compounds compared with the control.

Chromatography, High Pressure Liquid↗

[Effects of krestin (PSK) on drug-metabolizing enzymes with special reference to the activation of FT-207].

The effects of PSK on hepatic drug-metabolizing enzymes were investigated using Sarcoma 180-bearing and non-tumor-bearing ICR mice. PSK, an immunomodulator, has been commonly used in combination with tegafur for post-operative adjuvant chemotherapy. Tegafur is a typical masked compound transformed into 5-FU by the hepatic drug-metabolizing enzyme P-450. It has been reported that immunostimulants such as BCG and anaerobic Corynebacterium suppress the drug metabolism. PSK and Propionibacterium acnes were administered to mice inoculated s.c. with Sarcoma 180. It was demonstrated that Propionibacterium acnes had an effect of inhibiting these enzymatic activities, especially the amount of P-450 and cytochrome b5 and aminopyrine demethylation. On the other hand, PSK had no influence on the drug-metabolizing enzymes. Propionibacterium acnes was shown to decrease the 5-FU level in organs and sera of mice given FT-207 orally. By contrast, PSK showed no difference in 5-FU level compared to controls, indicating that PSK had no inhibitory effect on the activation of FT-207 by hepatic drug-metabolizing enzymes.

Aminopyrine↗

[Retroperitoneal schwannoma: a report of two cases and review of the literature].

Two cases of retroperitoneal schwannoma, one malignant, and the other benign, are herein reported. The first case was a 71-year-old female with a complaint of dull right flank pain. CT scan showed a large mass, which occupied almost the whole right half of the abdominal cavity extraperitoneally, accompanied by a low density portion in its central part. Angiography showed several feeding arteries, such as intercostal arteries, lumber arteries, and so on. Many tortuous and thin irregular vessels were seen. Tumor excision was performed under the diagnosis of malignant retroperitoneal tumor. No surrounding invasion or metastasis were seen. The tumor had a thick capsule, and cut surface showed lobulated appearance. No adjuvant therapy was done. Histological diagnosis was low grade malignant schwannoma. She is alive and well 17 months postoperatively. The second case was a 64 year-old male. His tumor was found incidentally, when he underwent a close examination of his gastric ulcer. According to CT scan, it was located behind the left kidney, and had a diameter of 3.0 X 2.5 cm. The tumor was removed including the fascia of lateral edge of quadratus lumbolum muscle, where it was firmly attached to. Surgical specimen showed a doughnut like appearance, because of its marked central necrosis. It had a white and thick capsule. Histological diagnosis was benign schwannoma of two different types, Antoni A and B. He remains well 13 months after operation. The 113 benign cases and 55 malignant cases reported in Japan, including our cases, were reviewed and discussed.

Aged↗

Partial prevention of compactin (ML-236B) inhibition of in vitro hematopoiesis by dolichol and dolichyl phosphate.

We have reported that the exogenous addition of dolichyl phosphate (Dol-P) enhances the colony-forming capacities of early erythroid progenitors (BFU-E), late erythroid progenitors (CFU-E), and granulocyte-macrophage progenitors (CFU-GM) in adult mouse bone marrow, and that dolichol (Dol) enhances that of only CFU-E (Int. J. Cell Cloning 3:313, 1985). Compactin (2.5-10 microM), a specific inhibitor of mevalonate biosynthesis that causes a decrease of endogenous Dol biosynthesis, inhibited colony formation of CFU-GM. Exogenous addition of Dol-P partially prevented this inhibition, but Dol and the other mevalonate metabolites, such as cholesterol, coenzyme Q10, and isopentenyladenine, could not. In addition, we have found that the colony-forming capacity of CFU-E in fetal mouse liver was not enhanced by exogenous Dol or Dol-P. But the decrease of colony formation or DNA synthesis of fetal CFU-E in the presence of compactin was prevented by the exogenous addition of Dol or Dol-P.

Animals↗

[Detection of Chlamydia trachomatis with a direct specimen test (MicroTrack) in urethritis patients].

The urethral smear specimens from 197 male urethritis patients attending our department and 4 affiliated hospitals were examined for Chlamydia trachomatis between April, 1984 and May, 1985, using fluorescein-labeled monoclonal antibodies (Direct Specimen Test; MicroTrack, Syva Co., USA). C. trachomatis was detected in 7 (25.0%) out of 28 patients with gonococcal urethritis, and 83 (49.1%) out of 169 patients with nongonococcal urethritis. The detection rates were almost comparable to those of other reports that used the cell culture method. The direct test is a time-saving, non-culture method useful for the diagnosis of chlamydial infection.

Adolescent↗

Burst discharges of pontine reticular neurons in relation to forelimb stepping of thalamic and high spinal cats.

The paralemniscal pontine reticular neurons (PLRF) exhibited burst discharges when thalamic cats stepped on the moving treadmill, during stepping induced by mesencephalic locomotor region (MLR) stimulation, fictive locomotion by MLR stimulation after immobilization and during MLR stimulation after transection at the C2 level. These results imply that MLR stimulation can evoke burst discharge within the brainstem which may obtain alternating limb movements via descending tract to the cervical cord.

Animals↗

Evidence for unique homologous peptide sequences around the glycosylated seryl and threonyl residues in polysialoglycoproteins isolated from the unfertilized eggs of the Pacific salmon Oncorhynchus keta.

Structures of glycopeptides obtained by exhaustive Pronase digestion of high molecular weight (1.7 X 10(5)) salmon egg polysialoglycoprotein have been elucidated. Six principal glycopeptides isolated by gel chromatography and DEAE-Sephadex A-25 chromatography in the absence or presence of borate ion were analyzed for their carbohydrate and amino acid composition, as well as amino acid sequence, and found to be of two distinct types: glycotripeptides, Thr*-Ser*-Glu, and glycotetrapeptides, Thr*-Gly-Pro-Ser, where an asterisk indicates the amino acid residues to which either the Gal beta 1----3GalNAc or Fuc alpha 1----3GalNAc beta 1----3Gal beta 1----4Gal beta 1----3GalNAc chain is attached. Their final yield corresponds to 64% of the original desialylated glycoprotein. In view of the simple amino acid composition of salmon egg polysialoglycoprotein (molar ratio Asp2Thr2Ser3Glu1Pro1Gly1Ala3) and the result of alkaline beta-elimination indicating three carbohydrate units linked to two of two threonine and one of three serine residues, a unique primary structure comprising repetitive sequences of the above two types of glycopeptides, which are interspersed by short nonglycosylated peptides consisting of alanine and aspartic acid, has been proposed for the core protein. The molecular secondary ion mass spectra of underivatized glycopeptides were used to obtain their structural information. The anomeric configuration of the proximal sugar-peptide linkages was proven to be alpha by proton nuclear magnetic resonance spectroscopy. This is the first systematic reported study of O-glycosidically linked glycopeptides by these instrumental methods.

Amino Acid Sequence↗

Separation of enkephalin-degrading enzymes from longitudinal muscle layer of bovine small intestine. Enzyme inhibition by arphamenine A.

The enkephalin-degrading enzymes, such as aminopeptidase, dipeptidyl aminopeptidase, dipeptidyl carboxypeptidase and carboxypeptidase, were purified partially by DEAE-cellulose column chromatography, using longitudinal muscle from bovine small intestine. These enzyme were inhibited by EDTA and o-phenanthroline. Several protease inhibitors of microbial origin, and synthetic compounds, were tested for their abilities to inhibit these enkephalin-degrading enzymes. Among them, arphamenine A, a new potent inhibitor for aminopeptidase B, was shown to be a useful compound in inhibiting all of the enkephalin-degrading enzymes in small intestine.

Aminopeptidases↗

Sepharose derivatives containing citric acid as affinity ligand. Purification of fumarase.

Six Sepharose derivatives, in which citrate was immobilized via methylene carbons, were prepared by coupling of the alpha- and beta-isomers of citrylpolymethylenediamine to Sepharose. The purification of fumarase from pig heart was dependent on the length of the spacer arm, but not on the isomeric configuration of the immobilized citrate. Gels having six methylene carbons had the largest adsorption capacity for the enzyme and therefore were the most suitable for use in affinity columns for its purification. Affinity chromatography with these gels was followed by hydrophobic interaction chromatography on an octamethylenediamine-Sepharose column.

Animals↗