Search PubMed⌕ Search

Biomedical subjects

N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 505 records · Page 28Linked to original sources

Epimerization kinetics of moxalactam in frozen urine and plasma samples.

The epimerization of moxalactam (LMOX) in frozen urine and plasma samples was studied during long-term storage. The R/S ratio at equilibrium [(R/S)eq] at -10 degrees C was similar in urine and in rat and human plasma ultrafiltrate but differed from that in water. The (R/S)eq values in human plasma and its ultrafiltrate differed slightly, while they were the same in rat plasma and in its ultrafiltrate. The difference for the human plasma and ultrafiltrate may result from differences in plasma protein binding between R- and S-epimers in the liquid region of the frozen plasma. The change of R/S ratio in frozen human plasma continued below the collapse temperature of LMOX aqueous solution, where the liquid region appeared still to exist as determined by NMR measurement. Consequently, the biological LMOX samples should be preserved at or below -70 degrees C to prevent changes in the R/S ratio.

Animals↗

Dose and dose-splitting effects of X-rays on lung tumour induction in mice.

This paper reports lung-tumour induction 12 months after single or split doses of X-rays in C3H/He male mice. The early proliferative response of lung cells after doses which induced lung tumours was also examined after single X-irradiation. The lung-tumour incidence tended to increase with increasing dose after a single irradiation and peaked at 5 Gy. At more than 10 Gy it decreased sharply to the control level. The mean tumour diameters tended to increase with doses up to 7.5 Gy and then decreased beyond 10 Gy. These results suggested that suppression of tumour growth reduced the tumour incidence at doses of over 10 Gy. The lung-tumour incidence decreased with increasing intervals between two equal doses of 2.5 or 5 Gy. The decrease was thought to be caused by the repair of the tumorigenic injury. However, the tumour incidence after two 2.5 Gy irradiations at 1 day intervals or two 5 Gy irradiations at 6 h intervals was higher than that observed after a single dose. This phenomenon was regarded as a progression of the tumorigenic injury. The labelling indices of the lung cells, determined using tritiated thymidine after a single irradiation, were higher than those of non-irradiated control cells. This response was delayed as the dose increased. The responses versus days after irradiation could be classified into three patterns on the basis of their peaks. The possibility that the larger delay after higher doses had some relation to the reduction of target cells for tumour incidence is suggested.

Animals↗

Angiographic study of induced cerebral aneurysms in primates.

Five cynomolgus monkeys treated with unilateral carotid ligation, renal hypertension, and beta-aminopropionitrile feeding were studied repeatedly by cerebral angiography to clarify the growth process of saccular cerebral aneurysms. Repeated angiography demonstrated saccular cerebral aneurysms in three of five monkeys; two aneurysms were found 15 months and a third 12 months after the operation. At autopsy, one saccular aneurysm was found to be bilocular in shape, and the others were unilocular. Fusiform aneurysms were also observed in four monkeys. Microscopic studies revealed the walls of the saccular aneurysms were very thin and consisted of fibrous tissue. In one aneurysm, the aneurysmal sac was almost obstructed by a well-organized thrombus. No evidence of intramural hemorrhage was found in any of the saccular cerebral aneurysms. The conversion of early aneurysmal changes into saccular aneurysms was found to occur abruptly, and no consistent growth rate was noted. The multiloculation of saccular aneurysms was closely related to the size of an aneurysm. The present study indicates that a saccular cerebral aneurysm may grow abruptly from one of several different kinds of early aneurysmal changes.

Aminopropionitrile↗

Non-T, non-B lymphoblastic lymphoma in two pigs.

The histological, immunological and ultrastructural observations on two cases of non-T, non-B lymphoblastic lymphoma are reported. Although the neoplastic cells had neither sheep erythrocyte (E) receptors for T lymphocytes nor surface membrane immunoglobulin (SIg) for B lymphocytes, terminal deoxynucleotidyl transferase (TdT) was demonstrated in the nuclei of many or some neoplastic cells. Ultrastructurally the neoplastic cells showed no specific features except desmosome-like junctions. The morphological and immunological findings suggest that the present cases are derived from immature lymphoid cells or stem cells of the bone marrow. The significance of the junctions is discussed and such structures may be common in various mesenchymal cells.

Animals↗

Malignant lymphomas of thymus origin in two sows.

Two cases of swine thymic lymphoma were investigated by electron microscopy and the immunoperoxidase method for terminal deoxynucleotidyl transferase (TdT), and furthermore sheep erythrocyte rosette assay was applied to one case. In case 1, immunoblastoid cells predominated and smaller cells were admixed with them. Many neoplastic cells were TdT-positive and formed rosettes with sheep erythrocytes at 4 degrees C, but about half of them formed rosettes at 37 degrees C. Ultrastructurally the neoplastic cells were characterized by highly irregular nuclei, poorly developed organelles and clustered dense bodies. The neoplasm in case 2 was composed of medium-sized to large cells and the latter predominated. A few of the neoplastic cells stained positively with anti-TdT serum. Ultrastructurally the neoplastic cells were characterized by nuclear convolution, narrow cytoplasmic bands and clustered dense bodies. The morphological features of thymic lymphomas were discussed in comparison with those of other swine lymphomas and lymphomas of other animals. Histological and immunological progression into T-immunoblastoid cells in case 1 was also discussed.

Animals↗

Immunohistochemical localization of c-myc oncogene product and EGF receptor in oral squamous cell carcinoma.

Subcellular distribution of c-myc oncogene product and EGF receptor in oral squamous cell carcinomas was examined by using immunohistochemical method. Immunohistochemy for c-myc oncogene showed three staining patterns. Reactive products were demonstrable in the nucleus, in the perinuclear cytoplasm with granular appearance and in the entire cytoplasm. Concomitant stainings of each reactive pattern were observed. Occasionally, the reactive product was strongly deposited on the chromatin under mitotic phase. EGF receptor positive cases were found in only 4 of 28 cases. Though reactive products were usually found in the cytoplasm, the cell surface staining was detected in the only one case. In this case, cells under mitotic phase were strongly stained. The fact that the strong staining both of c-myc and EGF receptor in cells under mitotic phase suggested the close relation between the expression of these genes and the proliferation of carcinoma cells.

Antibodies, Monoclonal↗

The cytoprotective effect of Trolox demonstrated with three types of human cells.

Trolox, a hydrophilic analogue of alpha-tocopherol, was reported to scavenge peroxyl radicals better than vitamin E in sodium dodecyl sulfate micelles and in liposomes. However, it was not known if Trolox protects human cells against oxyradical damage or if it acts as an antioxidant there. Here we demonstrate that Trolox prolonged substantially the survival of human ventricular myocytes and hepatocyte against oxyradicals generated with xanthine oxidase plus hypoxanthine, and prevented lysis of red cells exposed to an azo-initiator (2,2'-azo-bis(2-amidinopropane) HCl). Note that Trolox did not inhibit xanthine oxidase. In each cell type, the protection by Trolox was dose dependent and surpassed those given by such water-soluble antioxidants as ascorbic acid, superoxide dismutase, and (or) catalase, each examined at or near its optimal level in the same system. Using hepatocytes as a model, we further observed that Trolox reduced markedly the quantity of phospholipid conjugated dienes (a chemical imprint of oxyradical damage) in cells despite their exposure to oxyradicals. These data suggested that Trolox behaves as an antioxidant in cells as illustrated in hepatocytes.

Antioxidants↗

Elastic skeleton of intracranial cerebral aneurysms in rats.

In an attempt to clarify the developmental mechanism of cerebral aneurysms, we studied the elastic skeleton of experimentally induced cerebral aneurysms in rats under scanning electron microscopy after hot formic acid extraction followed by freeze-drying. We produced cerebral aneurysms in 19 rats by unilaterally ligating the common carotid artery, inducing renal hypertension, and feeding beta-aminopropionitrile fumarate. The first noted change was the loss of folds protruding from the internal elastic lamina. Morphologic changes of the internal elastic lamina, considered to be primarily responsible for aneurysmal formation, occurred after the loss or disintegration of the elastic skeleton of first the intima, then the media. In large aneurysms with thick domes, we found proliferation of elastic lamellae that may reduce the risk of rupture. It seems probable that the complex elastic skeleton of the arterial wall may account for the mechanical properties of the artery and that growth of an aneurysm occurs due to disintegration of the elastic skeleton and not simply to rupture of the internal elastic lamina. We believe that such changes in the elastic skeleton are a property of the functional state of the cells that produce elastin.

Animals↗

Study of the elastic skeleton of intracranial arteries in animal and human vessels by scanning electron microscopy.

We studied the elastic skeleton of major cerebral arteries in rats, monkeys, and one human using scanning electron microscopy after hot formic acid extraction followed by freeze-drying. For comparison, we also examined the thoracic aorta and femoral artery of rats. The cerebral arteries of rats had one distinct internal elastic lamina connected to the thin adventitia with sponge-like medial elastic tissue. This internal elastic lamina had fenestrations, which we found to be less frequent in cerebral arteries than in extracranial arteries, and fold-like protrusions into the lumen. This finding has not been recognized before. Such protrusions were more prominent in cerebral arteries than in extracerebral arteries. At the apical intimal pad, the internal elastic lamina appeared to be continuous, making a honeycomb-like structure. The folds and fenestrations were numerous at the apex. There were no essential differences among species. Our study shows that the internal elastic lamina is not a simple sheet but part of the complicated architecture of the elastic tissue of the vessel wall. These differences in the elastic skeleton, including fenestrations and fold-like structures, in various sites of different arteries may explain the development of various localized vascular diseases.

Animals↗

An analysis of experimental radiation carcinogenesis with model setting for competing risks.

The mean life span of animals killed by a specific type of tumor and the incidence of that particular tumor are influenced by competing risks. A parametric approach for censored samples was applied to correct for the competing risks. The life span distribution under each risk wherein the other risks were thought to be eliminated is assumed to be a Weibull distribution. Our data were from an experiment on tumor induction by X-rays in mice: whole body irradiation with 600 R; head with 800 R; trunk with 800 R; or lower body with 800 R. Analysis of the results shows that the mean appearance time of malignant lymphomas was accelerated by whole body irradiation. Acceleration of lung tumors was relatively large after trunk irradiation. Mammary tumors were accelerated by whole body, trunk or lower body irradiation.

Animals↗

Pathology of experimental chlamydiosis in chicks.

Twelve one-day-old chicks were experimentally inoculated with Chlamydia psittaci derived from turkeys. Acute chlamydial septicemic lesions were induced by the inoculation into the air sac and trachea. No lesions were produced by the esophageal injection. Clinically, the affected chicks showed emaciation and mouth breathing, and were inactive while some birds died. Grossly, they had hepatomegaly, splenomegaly and airsacculitis. Histopathologically, fibrinopurulent airsacculitis, pneumonia and bronchitis, multiple fibrinous serositis in the hepatic and splenic capsules, peri- and epicardium, and mesenterium, focal endoarteritis in the aortae, activation of reticuloendothelial cells in the spleen, and hepatic necrosis were noted. Immunohistochemically, chlamydial antigen granules were present in the cytoplasm of epithelial cells of the respiratory system, hepatocytes, macrophages in the air sac, lung, serous membrane, liver, spleen, aortae, reticuloendothelial cells in the spleen, and mesothelial cells in various organs or tissues. Chlamydial multiplication in the cells of the organs or tissues involved was preceded to form the lesions.

Air Sacs↗

Change in the growth hormone (GH) response to GH-releasing factor (GRF) caused by exogenous GH in short children.

To determine whether exogenous GH induces feedback of GH release in children, growth hormone-releasing factor (GRP) tests were performed before and after 10-day GH administration. Sixteen non-obese short boys, aged 5-14 yr, with normal GH response to pharmacological tests were studied. Mean basal and peak serum GH levels in GRF tests before and after exogenous GH were not significantly different. The subjects were divided into two groups, A and B, according to the percent change in integrated areas under the GH curves in GRF tests (GH AUC) before and after 10-day GH administration. Group A consisted of 6 boys with decreased GH AUC and group B consisted of 10 boys with increased GH AUC. Mean peak GH in GRF tests and mean GH AUC were significantly higher before exogenous GH in group A than in group B. The boys in group A were all prepubertal, while 4 boys in group B had begun their early pubertal change. The mean age in group A (7.8 +/- 1.8 yr) was significantly lower than that of group B (11.9 +/- 2.4 yr). GH AUC before exogenous GH showed a significant correlation with the percent change in AUC (= -0.742, p less than 0.01). These data demonstrated that the exogenous GH suppressed the GH response to GRF in prepubertal children with good response to GRF before exogenous GH, while it exaggerated the GH response to GRF in older children with relatively poor response before GH.

Adolescent↗

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↗

Transsphenoidal approach to infrasellar tumors involving the cavernous sinus.

The authors review their 2-year experience with a rhinoseptal transsphenoidal approach to skull-base tumors of various pathologies involving both the sphenoid and cavernous sinuses. Eight patients with cranial nerve palsies attributable to compression of the contents of the cavernous sinus and/or optic canal are included in this report. Among these patients, a total of 17 cranial nerves were affected. Postoperative normalization was achieved in eight nerves, significant improvement in seven nerves, and no improvement in two nerves. There were no operative complications of aggravation of cranial nerve palsies in this series. In spite of the limited operating field, the results demonstrate the effectiveness and safety of this approach. The authors recommend that this approach be considered before more aggressive surgery is undertaken.

Adult↗

Effects of the new phosphodiesterase inhibitor griseolic acid on insulin release in rat pancreatic islets.

A new cyclic AMP phosphodiesterase inhibitor, griseolic acid (CAS 79030-08-3), in a dose-dependent manner increased insulin release and cyclic AMP level in rat pancreatic islets in the presence of 5.5 mmol/l glucose. Griseolic acid (0.26 mmol/l) or 3-isobutyl-1-methylxanthine (IBMX) (1 mmol/l) enhanced insulin release and cyclic AMP level both in the presence of 5.5 and 16.7 mmol/l glucose (no significant difference). In perifusion system, 45Ca++ efflux and insulin release showed a monophasic increase when the islets were exposed to 1.3 mmol/l griseolic acid or 1 mmol/l IBMX in the presence of 5.5 mmol/l glucose (no significant difference). In a cell-free system, griseolic acid had a stronger inhibitory effect on cyclic AMP phosphodiesterase activity than IBMX, has a stimulatory effect on insulin release through an increase of cyclic AMP by inhibiting phosphodiesterase in pancreatic islets, but it might not cross the plasma membrane easily.

1-Methyl-3-isobutylxanthine↗

Degeneration and ossification of the yellow ligament in unstable spine.

Lumbar yellow ligaments were obtained from 20 cases of lumbar spinal canal stenosis and 20 cases of degenerative olisthesis with slippage of more than 3 mm. The ligaments were stained with safranin-O, von Kossa, and immunohistochemical staining methods (S-100 protein). In the unstable group the safranin-O staining was more intense, microscopic ossification and chondroblasts were noted more frequently, and S-100 protein was more abundant. These findings show that instability of the lumbar spine accelerates degeneration and chondrometaplasia of the yellow ligament, which may lead to the enchondral ossification of the ligament.

Adult↗

[A case of B-cell non-Hodgkin's lymphoma with prominent splenomegaly and high serum titer of cold agglutinin].

The case of 37-year-old male with non-Hodgkin's lymphoma with prominent splenomegaly is presented. The spleen that was removed for analysis had a weight of 2690 grams and a section inspection revealed multiple, whitish, small nodules that were disseminated throughout the entire spleen. It was microscopically demonstrated to be a B-Cell lymphoma of diffuse, medium-sized cells and an IgM.kappa Type. This case also was complicated by a high serum titer of cold agglutinin that was decreased by chemotherapy.

Adult↗