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Biomedical subjects

H Sugihara

Publications and source records attributed to H Sugihara.

At least 361 records · Page 20Linked to original sources
PubMed1988

Physiological and biochemical properties of a kallikrein-like enzyme from the venom of Vipera aspis aspis (aspic viper).

A kallikrein-like enzyme was isolated from the venom of Vipera aspis aspis by Sephadex G-75, Q-Sepharose and Heparin-Sepharose CL-6B column chromatography. The purified enzyme is a glycoprotein with a mol. wt of 43,000 and an isoelectric point of 4.1. The enzyme possesses arginine ester hydrolase activity, but no proteolytic activity against either dimethylcasein or fibrinogen. The reaction mixture of the enzyme and bovine plasma induced contraction of the isolated rat uterus, suggesting that the enzyme releases kinin from the plasma constituent. The amount of enzyme, which releases an equal amount of kinin corresponding to 1 nmole of bradykinin per min, is 2.36 mg. Additionally, the kallikrein-like enzyme demonstrated capillary permeability-increasing activity and hypotensive activity. A synthetic kininogen analog, Ser-Leu-Met-Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-Ser-Val-Gln-Val-Ser, was cleaved by the enzyme to release bradykinin and kallidin, also indicating that the enzyme has a kallikrein-like activity. Uterine contraction, capillary permeability-increasing activity and arginine ester hydrolase activity were inhibited by diisopropyl fluorophosphate, suggesting that the serine hydroxyl group is essential for enzymatic and biological activities. Antithrombin III and heparin, serine-protease inhibitors found in plasma had no inhibitory effect on these activities of the purified enzyme. The amino acid sequence of the NH2 terminal region of the enzyme has similarities with kallikrein-like enzymes from other snake venoms and with porcine pancreatic kallikrein.

Amino Acids↗
PubMed1988

Beta-fibrinogenase from the venom of Agkistrodon p. piscivorus.

1. Beta-fibrinogenase was isolated from the venom of Agkistrodon p. piscivorus by column chromatography on Sephadex G-100, DEAE-Sephacel and by chromatofocusing, with a yield of 2.5 mg of purified enzyme from 1 g of crude venom. 2. The enzyme was homogeneous by SDS and non-SDS disc electrophoresis on polyacrylamide gel at pH 8.3. 3. Beta-fibrinogenase is a glycoprotein possessing both TAME hydrolase and kinin-releasing activities. 4. A mol. wt of approximately 33,500 and an isoelectric point 4.5 was determined. 5. The enzyme is stable to heat treatment and to a pH range of 2-10. 6. Beta-fibrinogenase activity is inactivated by DFP, suggesting that serine is involved in the enzymatic activity. 7. The Michaelis constant (Km) of this enzyme for TAME and inhibition constant (Ki) for DFP were found to be 7.04 X 10(-3) and 4.13 X 10(-3) M, respectively.

Amino Acid Sequence↗
PubMed1988

Biological study of muscle degenerating hemorrhagic factor from the venom of Vipera aspis aspis (aspic viper).

1. A hemorrhagic factor was isolated from Vipera a. aspis venom by gel filtration, ion-exchange chromatography and affinity chromatography. 2. Molecular weight of the purified factor was determined to be 67,000 Da, which was composed of 552 amino acid residues. 3. The minimum hemorrhagic dose (MHD) was measured to be 0.11 micrograms per mouse with subcutaneous injection. The hemorrhagic activity was inhibited by chelating agents and reductant. 4. The hemorrhagic factor possesses proteolytic activity against dimethylcasein. 5. Serum creatine phosphokinase level was rapidly increased within 30 min following injections of this preparation into the mice thighs. 6. Actin, one of the main components of muscle fiber, is apparently digested by the hemorrhagic factor. The pathological findings are further reported in this paper.

Amino Acids↗
PubMed1988

Kallikrein-like enzyme from Crotalus ruber ruber (red rattlesnake) venom.

1. A kallikrein-like enzyme was isolated and characterized from the venom of Crotalus ruber ruber (red rattlesnake). 2. The kallikrein-like enzyme was shown to be homogeneous as demonstrated by a single band on acrylamide gel electrophoresis, isoelectric focusing, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunodiffusion and reverse-phase (RP) HPLC. 3. The enzyme has a molecular weight of 31,000 and isoelectric point of 4.6. It consists of 271 total amino acid residues, 24% of which are acidic amino acids. 4. Specific esterolytic activities of the kallikrein-like enzyme on N-tosyl-L-arginine methylester (TAME) and N-benzoyl-L-arginine ethylester (BAEE) are 109.5 and 23.6 mumol/min/mg, respectively. 5. The enzyme differs from trypsin as the soybean trypsin inhibitor does not inhibit the enzyme's action. Diisopropylfluorophosphate (DFP) inhibits the enzyme, suggesting that the serine hydroxyl group is important for enzyme activity. 6. The enzyme is not lethal at 15 micrograms/g in mice and has no hemorrhagic activity, yet the injection of the purified enzyme intradermally, produced capillary permeability-increasing activity as shown by the use of Evans blue dye, and immediate drop in blood pressure. It also contracted the rat uterus.

Amino Acids↗
PubMed1988

Testicular tumors in non-twin brothers from a consanguineous marriage.

Malignant testicular tumors occurring in non-twin brothers are reported. Both of the brothers suffered from amentia and epilepsy and were the product of a consanguineous marriage. One brother presented with teratocarcinoma and the other seminoma. With a review of the literature, genetic roles in the etiology of testicular neoplasia are discussed.

Adolescent↗
PubMed1988

Effect of testosterone on growth hormone secretion in female rats during a continuous infusion of growth hormone releasing factor.

The effect of testosterone on growth hormone (GH) secretory pattern during a 6-hour continuous infusion of human GH-releasing factor (GRF) (1-44) NH2 was observed in unrestrained adult female Wistar rats. Rats had been ovariectomized or sham operated 6 weeks previously. Three weeks after the ovariectomy, the rats received sesame oil or testosterone propionate at a dose of 1 or 2 mg s.c. daily for 21 days. All rats were provided with two indwelling cannulae: one in the right atrium for undisturbed blood collection and the other in the inferior vena cava for vehicle or GRF infusion. Vehicle or GRF was administered by an infusion pump at a dose of 50 ng/kg/min for 6 h. Serial blood specimens were obtained every 20 min. Sham-operated adult female Wistar rats exhibited a high-frequency, low-amplitude pulsatile GH secretion during a 6-hour vehicle infusion. When they received a 6-hour continuous infusion of GRF, the amplitudes of GH pulses and baseline GH values were markedly augmented, but the pulse frequency remained unaltered. The GH secretory pattern during a 6-hour vehicle infusion among ovariectomized rats was similar to that of sham-operated female rats, whereas the magnitude of elevation of GH pulse and baseline level in ovariectomized rats were significantly lower than in sham-operated rats. The ovariectomized female rats that had received 2 mg testosterone for 21 days showed a low-frequency, regularly timed, high-amplitude pulsatile GH secretion, and GH values during the intervening period were low. This GH secretory pattern was indistinguishable from that in adult male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

(R)-3-[(S)-1-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5- tetrahydro-1,5-benzothiazepine-5-acetic acid (CV-5975): a new potent and long-lasting inhibitor of angiotensin converting enzyme.

The synthetic design and the biological activities of structurally new angiotensin converting enzyme (ACE) inhibitors, (R)-3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid derivatives, are described. A number of compounds in this series showed potent ACE inhibitory activity in vitro and in vivo. Structure-activity studies indicated that a piperidyl moiety on the amino group at the 3-position in this series conferred long-lasting ACE inhibitory activity and that the duration of activity depended on the length of the carbon chain in the 1-carboxy-omega-(4-piperidyl)alkyl group. (R)-3-[(S)-1-carboxy-5-(4-piperidyl)-pentyl]amino-4-oxo-2,3,4,5-tetrahydro- 1,5-benzothiazepine-5-acetic acid (CV-5975) was selected as the most promising ACE inhibitor for further studies because of its marked inhibitory activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Inhibition of angiotensin converting enzyme by (R)-3-[(S)-1-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2,3,4,5-tetra- hydro-1,5-benzothiazepine-6-acetic acid (CV-5975), a non-sulfhydryl compound.

CV-5975, (R)-3-[(S)-1-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo- 2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid, was found to inhibit rabbit lung angiotensin converting enzyme (ACE) activity with an IC50 of 3.1 x 10(-9) M and a Ki of 2.6 x 10(-9) M, inhibit the angiotensin I (A-I)-induced contraction of the guinea pig ileum with an IC50 of 1.3 x 10(-8) M, and augment the bradykinin (BK)-induced contraction of the ileum with an AC50 of 9.2 x 10(-10) M. The activity of CV-5975 was comparable to or slightly more potent than that of enalaprilat. The overall inhibition constant (Ki*), calculated from a steady-state analysis of enzyme reactions, was 4.4 x 10(-12) M for CV-5975; this indicates that the inhibition was about 5 times more potent than that of enalaprilat (2.0 x 10(-11) M). In rats, CV-5975 (0.03 and 0.3 mg/kg, i.v. and 3 and 10 mg/kg, p.o.) inhibited the A-I-induced pressor action more potently and for a longer period than did the corresponding doses of enalaprilat and enalapril. CV-5975 and enalapril (3 mg/kg, p.o.) augmented the BK-induced depressor action to a similar extent. In dogs, CV-5975 (0.3 and 1 mg/kg, p.o.) markedly inhibited the A-I-induced pressor action in a dose related manner, and the duration of this inhibitory activity was longer than with the corresponding doses of enalapril. These data provide evidence for the proposal that CV-5975 is a highly potent and long lasting ACE inhibitor.

Angiotensin I↗
PubMed1988

[Primary intracranial malignant melanoma associated with nevus of Ota: a case report].

A case of intracranial malignant melanoma associated with nevus of Ota is presented. A 77-year-old man was admitted to the department of neurosurgery, Fukui Medical School on June, 1985 because of developing disturbed consciousness. The physical examination on admission revealed pigmented lesion diagnostic of the nevus of Ota, anisocoria (R greater than L) and left hemiparesis. Computed tomographic (CT) scans demonstrated a high density mass in the left temporal lobe and the mass was homogenously enhanced after the injection of contrast agent. Left common carotid angiogram showed elevation of the middle cerebral artery and a slight vascular blush. Subtotal removal of the dark-colored tumor within the left temporal lobe and biopsy of the nevus were performed. Histopathological examination of the tumor revealed malignant melanoma and that of the skin biopsy was consistent with a nevus of Ota. Postoperatively DTIC, ACNU and vincristine were administered intravenously but the patient died three weeks after operation. At autopsy, widespread black pigmentation of the leptomeninges, communicating with the pigmented tumor in the left temporal lobe, covered the base of the brain and spinal cord. No melanoma was found outside the central nervous system. Primary intracranial melanoma associated with nevus of Ota is rare and only 6 cases have been reported in the literature. In this paper, primary intracranial melanoma associated with nevus of Ota and some other subjects are discussed.

Aged↗
PubMed1988

[A case of cystic changes in a giant leiomyoblastoma of the stomach].

A 44-year-old male was admitted to hospital with a complaint of abdominal distention. A CT scan revealed a giant multicystic mass in the abdominal cavity, a tumor that measured 34 cm in diameter, which had risen from the gastric body and grew in an exophytic fashion with a stalk. Histologic findings exhibited a malignant leiomyoblastoma with cellular pleomorphism and a intracytoplasmic cystic change, which included disseminated nests of immature small round cells. After excisional surgery, the patient has had no sign of a recurrence for the past two years.

Adult↗
PubMed1988

[Value of exercise echocardiography in evaluating left ventricular systolic function in mitral stenosis].

Exercise echocardiography was performed for 34 patients with mitral stenosis (MS) to evaluate left ventricular (LV) systolic function. The patients were categorized in three groups according to the work loads attained: Group I, 14 patients who attained 25 watts; Group II, 10 patients, 50 watts; and Group III, 10 patients, 75 watts. Among these groups, there were no statistical differences between the resting echocardiographic LV systolic function and their cardiac catheterization data. Resting LV end-diastolic and end-systolic dimensions (EDD and ESD) did not differ by group. During exercise, EDD and ESD decreased significantly in all groups, but ESD at the maximum exercise in Group I was greater than those of the other groups. The percent fractional shortening of the left ventricle (%FS) decreased significantly with exercise in Group I, while it increased significantly in the other groups. The mean velocity of circumferential fiber shortening (mean Vcf) increased significantly in all groups, but the extent was least in Group I. The exercise-induced changes in %FS (delta %FS) and mean Vcf (delta mean Vcf) correlated closely with exercise duration (r = 0.80, r = 0.73), but this was not the case in the mitral valve area. Postoperatively, exercise echocardiography was also performed for 14 patients with mitral stenosis; two of seven patients in Group I, four of five in Group II, and two in Group III showed significant improvement in exercise tolerance after surgery. However, the other six patients showed no change in their exercise tolerance. The former patients had positive values in delta %FS and more than 0.5 circ/sec in delta mean Vcf during pre-operative evaluations, while except one patient, those who did not improve had negative delta %FS values and less than 0.5 circ/sec in delta mean Vcf. It was concluded that the change in LV systolic function during exercise echocardiography reflects LV functional reserve in patients with MS, and provides valuable information for evaluating the severity of, indications for and benefits from surgery for MS.

Blood Pressure↗
PubMed1988

Unilocular fat cells in three-dimensional collagen gel matrix culture.

Three-dimensional culture with collagen gel, developed recently for the in vitro study of some mammalian cells in a more physiological condition than a monolayer culture, was applied for a biological study of unilocular fat cells. Successfully embedded in the gel, the unilocular fat cells were shown to be able to keep their cellular function and actively proliferate. These findings confirm that unilocular fat cells do undergo proliferation under in vitro conditions as demonstrated in monolayer culture.

Adipose Tissue↗
PubMed1987

Biochemical characterization of hemorrhagic toxins with fibrinogenase activity isolated from Crotalus ruber ruber venom.

Three hemorrhagic toxins with proteolytic activity were isolated from the venom of Crotalus ruber ruber (red rattlesnake). Molecular weights of HT-1, HT-2, and HT-3 were 60,000, 25,000, and 25,500, respectively. Although HT-3 was a basic protein, HT-1 and HT-2 were slightly acidic proteins. Total amino acid residues were 482,207, and 221 for HT-1, HT-2, and HT-3, respectively. Protease activity of all the toxins was inhibited in the presence of EDTA or o-phenanthroline, suggesting that the toxins are metalloproteins. Analyses for various metals by inductively coupled plasma-atomic emission spectrometry indicated that sodium, potassium, zinc, and calcium atoms were present in significant quantities. With all three toxins, there was roughly 1 mol of zinc to 1 mol of protein; the results for calcium were not consistent. All three hemorrhagic toxins degraded the A alpha chain of fibrinogen, while HT-1 also degraded the B beta chain. Although fibrinogen was degraded by the three toxins, no clots were observed, indicating that the proteolytic specificities of the three toxins were different from those of thrombin. The hemorrhagic toxins increased creatine kinase activity in mice serum, indicating muscle damage, which was substantiated by histological examination.

Amino Acids↗
PubMed1987

Cell proliferation and differentiation in intramucosal and advanced signet ring cell carcinomas of the human stomach.

In order to study the progression of signet ring cell carcinomas in the human stomach, we compared cell proliferation and differentiation between small and large intramucosal cancers, and between intramucosal and advanced cancers. Fine-structurally, signet ring cells were differentiated to 3 cell types: a foveolar, a glandular and an intestinal type. In the mucosa, the foveolar-type cells and glandular-type cells were distributed at the superficial and the deep zone, respectively. In the small mucosal cancers, intestinal-type cells were rare and a layered structure was often seen. In this structure, the mode of cell production resembled that in the normal gastric mucosa; the foveolar-type signet ring cells in the superficial layer were not proliferative and the proliferating cells were small cells in the middle layer and a few glandular-type cells in the deep layer. In the large mucosal and advanced cancers, intestinal-type cells and proliferating small round cells were often distributed throughout the depth of the mucosa, and signet ring cells of the foveolar type were also proliferative. These findings indicated that large part of the signet ring cell carcinomas initially form the layered structure and that it becomes indistinct while intestinal-type cells appear as the tumour grows. However, we found several small advanced cancers, lacking both the layered structure and the intestinal-type cells. These cancers appear to start without the layered structure and progress very rapidly.

Adenocarcinoma, Mucinous↗