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Biomedical subjects

F Hazama

Publications and source records attributed to F Hazama.

At least 73 records · Page 4Linked to original sources
PubMed1990

Effects of blood coagulation factor XIII on the development of experimental cerebral aneurysms in rats.

Pathological and experimental studies have shown that cerebral aneurysms develop in part as a result of injury to the blood vessel wall. One of the peculiar aspects of aneurysm development is a defective proliferative or healing response to such injury. To examine this phenomenon, blood coagulation Factor XIII, which is known to enhance the healing process of wounds in general, was given to rats to induce experimental cerebral aneurysms. The rats were subjected to ligation of one common carotid artery and induction of hypertension, and were fed beta-aminoproprionitrile. Two weeks thereafter, Factor XIII was injected intravenously daily for 5 days (10 U/100 gm body weight/day). Twelve days after the start of Factor XIII injections, the rats were sacrificed and examined under light and electron microscopy. In seven of 12 bifurcations which developed small aneurysms, prominent intimal thickening was observed in the aneurysm lumen. In the most advanced cases, the aneurysm lumen was completely filled with proliferated smooth-muscle cells and collagen. In five of nine bifurcations that showed no aneurysm development, apparent intimal thickening was found at the site where aneurysms might be expected to grow. In the group of rats studied for induction of cerebral aneurysms but not given Factor XIII, none of 11 bifurcations with or without aneurysms showed such intimal thickening. The results indicated that the proliferative response at the sites of aneurysm development was modified by exogenous Factor XIII.

Animals↗
PubMed1989

Establishment of the experimental conditions for inducing saccular cerebral aneurysms in primates with special reference to hypertension.

To find out the optimum experimental conditions for the induction of saccular cerebral aneurysms in primates, various procedures for inducing renal hypertension were used in cynomolgus monkeys treated with ligation of unilateral carotid artery and beta-amino-propionitrile feeding. Animals were divided into four groups. In the first group, both kidneys were simultaneously compressed with a figure-eight ligation. In the second group, the kidneys were ligated at an interval of one week. In the third and fourth groups, posterior branches of both renal arteries were ligated at the same time, or at an interval of one week, respectively. Hypertension about 200 mmHg was produced only in the last group and aneurysms were noted in more than half of these hypertensive animals. The best procedure for renal hypertension to induce cerebral aneurysms was proved to be ligation of the posterior branches of both renal arteries at an interval of one week. We can conclude that lasting severe hypertension is essential for inducing cerebral aneurysms in monkeys.

Animals↗
PubMed1989

Histopathological study of induced cerebral aneurysms in primates.

Experimental cerebral aneurysms in monkeys induced by treating them with unilateral carotid ligation, renal hypertension, and beta-aminopropionitrile feeding were studied macroscopically and with light microscopy. Macroscopically, 13 cerebral aneurysms were observed in six of seven monkeys. Microscopically, the elastic lamina and the media ended around the beginning of the aneurysms. The thin aneurysmal walls consisted of fibrous connective tissues. All findings were generally in accordance with spontaneous lesions in humans. The induced cerebral aneurysms in primates are thought to be a suitable experimental model to clarify the pathogenesis of the disease.

Aminopropionitrile↗
PubMed1988

Lysosomal enzyme activities in the cerebral microvessels in spontaneously and renal hypertensive rats.

In an attempt to clarify the role of lysosomal enzymes in the developmental mechanisms of the changes of cerebral microvessels under hypertensive conditions, the activities of acid phosphatase, N-acetyl-beta-glucosaminidase, and beta-glucuronidase in the isolated microvessels from the cerebral cortex of spontaneously and renal hypertensive rats were biochemically studied. The activities of all the enzymes were higher than those in normotensive control animals, although there was a variation in intensity according to the age and kind of enzymes. The enzyme activities in spontaneously hypertensive rats showed a tendency to increase with advancing age. Hypertension seems to increase activities of lysosomal enzymes in cerebral microvessels, and this activation may in turn play a role in the development of further hypertensive cerebrovascular and cerebral changes.

Acetylglucosaminidase↗
PubMed1988

Effect of hypertension on lysosomal enzyme activities in aortic endothelial cells.

In order to obtain information about the changes in lysosomal enzyme activities in arterial endothelial cells under hypertensive conditions, a biochemical study was performed on 5 lysosomal enzymes, acid phosphatase, N-acetyl-beta-glucosaminidase (NAGase), cathepsin B, cathepsin D and beta-glucuronidase, in endothelial cells isolated by an enzymatic technique from the aorta of spontaneously and renal hypertensive rats, and normotensive control rats. The aortic endothelial cells in the old spontaneously and the renal hypertensive rats showed increased activities of enzymes examined in comparison with those in the age-matched control rats. Endothelial cells in young spontaneously hypertensive rats did not show any elevated enzyme activities compared with those in the controls, and the enzyme activities tended to increase with aging. From this, it is deduced that hypertension activates lysosomal enzyme activities in aortic endothelial cells. The differences in the activities of NAGase, cathepsin B and cathepsin D between hypertensive and control animals increased markedly with advancing age. These activated lysosomal enzymes seem to be involved in the developmental mechanism of arterial endothelial cell injury in hypertension and in further development of hypertensive vascular changes.

Acetylglucosaminidase↗
PubMed1988

Involvement of internal elastic lamina in development of induced cerebral aneurysms in rats.

To elucidate the role of the internal elastic lamina in the development of cerebral aneurysm, the bifurcation of the anterior cerebral artery and olfactory artery was histologically studied in control and experimental rats treated with unilateral carotid ligation and renal hypertension. Various stages of aneurysm formation were compared, and it was found that early aneurysmal changes were always present just distal to the apical intimal pad on the anterior cerebral artery side. The internal elastic lamina was thinned and fragmented just distal to the pad even in the very early stage of aneurysm formation when the medial layer was still present. In control rats, the internal elastic lamina had a tendency to thin and fragment at the site where aneurysms would develop in experimental rats. Our study shows that changes of the internal elastic lamina were present just distal to the pad even in control rats, which never develop cerebral aneurysms. Under hemodynamic stress augmented by experimental treatments, further degenerative changes of the internal elastic lamina and involvement of the medial layer are considered to occur and result in aneurysm formation there.

Animals↗
PubMed1988

Functional and histological changes in mesenteric arteries and aortas from monkeys fed a high cholesterol diet.

Treatment of Japanese monkeys for 8 months with a high fat, high cholesterol diet produced atherosclerotic lesions in the aorta and mesenteric arteries, such as fatty dots, streaks and plaques, intimal thickening with accumulation of spindle-shaped cells and macrophages and endothelial cell flattening. Contractile responses of mesenteric arteries from control and atherosclerotic monkeys to electrical stimulation of adrenergic nerves, norepinephrine and angiotensin II did not differ, whereas contractions caused by serotonin in the atherosclerotic monkey arteries were significantly greater. Ketanserin and cinanserin suppressed the serotonin-induced contraction. Relaxations caused by adenosine and K+ (5 mM) were moderately attenuated in atherosclerotic monkey mesenteric arteries, and those by acetylcholine were reduced only slightly or not affected in the arteries or aortas. Relaxations of control and atherosclerotic arteries in response to nitroglycerin, isoproterenol and prostaglandin I2 did not differ. The relaxant response to K+ was reversed to a contraction by ouabain. Acetylcholine-induced relaxations were dependent on the endothelium and suppressed by atropine. Diet-induced atherosclerosis appears to potentiate contractions mediated via serotonergic 5-HT2 receptors and to attenuate relaxations possibly caused by activation of the electrogenic Na+ pump in the smooth muscle cell membrane. Endothelium-dependent relaxations via muscarinic receptors would not evidently be affected in mesenteric arteries and aortas from atherosclerotic Japanese monkeys.

Animals↗
PubMed1987

Early changes in cerebral aneurysms in the internal carotid artery/posterior communicating artery junction.

In order to obtain information about preaneurysmal changes, the junction of the internal carotid artery/posterior communicating artery (ICA/PComA) in the circles of Willis in subjects with aneurysms at sites other than the junction, and in control subjects without aneurysms, were studied by light microscopy. Small evaginations and thinnings of the media with and without dilatation were observed at the apical areas of the forks with a significantly higher incidence in the aneurysm series than in the control, suggesting some predisposing factor in subjects with aneurysms. As well as funnel-shaped dilatations previously described as the only type of ICA/PComA preaneurysmal change, other more localized types were observed. All the small evaginations and about half of the thinnings and dilatations were observed at the apex in association with a medial gap, but the other half occurred at some distance from the apex. The thinned arterial wall showed degenerative changes of the elastic lamina and media. Intimal pads were observed at the apex, the ICA/PComA lateral angle and the ICA stem/branch curve. Their combination with preaneurysmal changes was more frequent in the aneurysm series in comparison with the control. Degenerative changes of the elastic lamina and media caused by hemodynamic stress due to branching structures including intimal pads are thus presumed to be the initial lesions existing prior to aneurysm formation.

Autopsy↗
PubMed1987

Experimental induction of cerebral aneurysms in monkeys.

Saccular cerebral aneurysms were successfully induced in two monkeys treated with ligation of the common carotid artery, experimental hypertension, and beta-aminopropionitrile feeding. The cerebral aneurysms developed on the large arteries at the base of the brain, such as the anterior communicating artery and the internal carotid artery at the origin of the posterior communicating artery. Because of the similarity of the monkey to man as a species, the present results strongly suggest the significance of postnatal aggravating factors in the development of cerebral aneurysms in man.

Aminopropionitrile↗
PubMed1986

Detection of metastatic medullary thyroid cancer with 131I-MIBG scans in Sipple's syndrome.

While 131I-meta-iodobenzyl guanidine (131I-MIBG) scanning has made possible the scintigraphic visualization of pheochromocytoma and neuroblastoma, an accumulation of this agent has recently been reported in medullary thyroid cancer. We present the case of a patient with Sipple's syndrome (multiple endocrine neoplasia type IIa), in whom we were able to identify distant metastases and local invasion of medullary thyroid cancer as well as primary thyroid tumour and right adrenal pheochromocytoma, using 131I-MIBG scans. This case highlights the usefulness of 131I-MIBG in the detection of metastatic medullary thyroid cancer and suggests that this agent may also be of therapeutic use in the treatment of tumours.

3-Iodobenzylguanidine↗
PubMed1986

Elastase, collagenase, and cathepsin D activities in the aortas of spontaneously hypertensive and renal hypertensive rats.

In an attempt to clarify the roles of proteases in the developmental mechanisms of hypertensive vascular lesions, changes in activities of aortic elastase, collagenase, and cathepsin D in spontaneously hypertensive rats (SHR) and renal hypertensive rats were biochemically investigated. In SHR, elastase activity initially showed a significant increase, once two-fold higher than that in the control; but the activity tended to decrease earlier than that in the control. In both SHR and normotensive control rats collagenase activities tended to increase with advancing age. The activity in SHR was two-fold higher than that in the control at all ages examined. In both younger SHR and normotensive rats cathepsin D activities proved to be increased with advancing age, while in old rats the activities tended to decrease. The activity in SHR was three- to fivefold higher than that in the control at all ages examined. In renal hypertensive rats, the activities of elastase, collagenase, and cathepsin D increased gradually with increasing blood pressure, at levels significantly higher than those in the control. These findings suggest that the metabolisms of proteins such as elastin and collagen, expressed by these enzyme activities, are accelerated under hypertensive conditions.

Aging↗
PubMed1986

Early changes of experimentally induced cerebral aneurysms in rats. Light-microscopic study.

The changes of the anterior cerebral artery/olfactory artery junction, one of the favorite sites of aneurysm formation, in rats treated with unilateral ligation of the common carotid artery and renal hypertension were investigated by light microscopy. The initial changes of aneurysm occurred not at the apex itself, but on the distal side of the major branch adjacent to the apex, at the intimal pad and the neighboring distal portion. Here the internal elastic lamina showed various degenerative changes and disappearance. The neighboring distal portion adjacent to the intimal pad showed a shallow depression associated with a thinning of the media due to a decrease of medial smooth muscle cells in number even in some control animals. Such degenerative changes of the internal elastic lamina and medial smooth muscle cells caused by hemodynamic stress due to branching structure, including intimal pads, augmented by the experimental treatment, are supposed to be the basis for aneurysm formation.

Animals↗
PubMed1985

Effects of the lysosomal fraction of polymorphonuclear leukocytes on proliferation of cultured vascular cells.

The effects of the lysosomal fraction isolated from polymorphonuclear leukocytes (PLF) on the growth of cultivated aortic medial smooth muscle cells (SMCs) and arterial endothelial cells (ECs) were studied by assaying DNA synthesis and counting the numbers of cells. PLF proved to promote the growth of cultivated SMCs and ECs. There was a positive correlation between an increase in DNA synthesis and the dose of PLF. The growth-promoting effect was observed in sparsely cultivated SMCs and ECs, in densely cultivated SMCs, but not in confluently cultivated ECs. The difference in response between SMCs and ECs seems to depend on their biological characteristics. Because a small amount of PLF showed potent growth-promoting activity in the presence of 10% fetal bovine serum which possesses a high protease blocking activity, the mechanism of this promoting activity is suggested to be independent of the proteases contained in PLF.

Animals↗
PubMed1985

5'-Nucleotidase activities in human fetus.

Specific 5'-nucleotidase (5'-N) activity in 17 human fetuses was systemically studied in order to get basic values of the enzyme activity. A wide spectrum of 5'-N activity among the organs was revealed. Very strong activity was found in placenta (42.62 +/- 19.24 nmol adenosine/mg protein/min), skeletal muscle (31.80 +/- 11.10) and skin (27.31 +/- 13.00); strong activity in liver (18.96 +/- 7.60), pituitary (15.06 +/- 6.13) and thyroid (12.69 +/- 4.47); moderate activity in lung (8.43 +/- 3.68), pancreas (8.20 +/- 2.26), small intestine (8.07 +/- 2.28), lymph node (7.26 +/- 2.22), thymus (7.06 +/- 2.52), spinal cord (5.86 +/- 1.96) and spleen (5.65 +/- 2.52), and weak activity in testis (4.02 +/- 0.79), heart (3.95 +/- 1.22), adrenal (3.46 +/- 1.68), kidney (3.16 +/- 0.83), ovary (3.16 +/- 0.72), aorta (2.98 +/- 1.20), cerebellar hemisphere (2.28 +/- 1.09) and frontal lobe of the cerebrum (1.49 +/- 0.54). These data are the first to be reported on specific 5'-N activity in the human fetus. The significance of the wide range of 5'-N activity among the organs, and future aspects on the study of 5'-N activity with respect to cell differentiation, maturation, development, aging or malignant transformation were discussed.

5'-Nucleotidase↗
PubMed1985

Alpha fetoprotein and carcinoembryonic antigen producing hepatocellular carcinoma. A case report studied by immunohistochemistry.

Hepatocellular carcinoma (HCC) showing marked elevation of serum alpha fetoprotein (AFP) (maximum; 70942.0 ng/ml at the end stage) and serum carcinoembryonic antigen (CEA)(maximum; 7368.4 ng/ml at the end stage) was surgically resected. In the resected liver, there were two different tumor nodules which were adjacent to each other but clearly separated by a thin connective tissue. One of the nodules was a well differentiated and the other was poorly differentiated HCC. Immunoperoxidase study revealed that both CEA and AFP were localized in the tumor cells of the poorly differentiated HCC. This is the first report which clearly proved CEA synthesis in the cells of HCC. Serial staining showed that there was simultaneous synthesis of CEA and AFP in some of the tumor cells.

Aged↗