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Biomedical subjects

S Higashi

Publications and source records attributed to S Higashi.

At least 91 records · Page 5Linked to original sources

Ultrastructure of the rat periodontal ligament as observed with quick-freeze, deep-etch and replica methods: arrangement of collagen and related structures.

The ultrastructure of the periodontal ligament of rat molars was examined with the quick-freeze, deep-etch replica methods. It was mainly composed of elongated fibroblast-like cells and 40- to 50-nm-wide collagen fibrils that are arranged parallel to one another to form fibers approximately 1 micron in width. Collagen fibrils are composed of 10-nm-wide substructures that may run helically against the long axis of the fibril. Numerous rod-like structures ('rods') approximately 10 nm in width are present around the collagen fibrils. Individual or groups of rods span spaces between neighboring collagen fibrils to interconnect them. The surfaces of the fibroblast-like cells are also connected to the nearest collagen fibrils through the rods. In place, strands with a thickness similar to that of the rods were seen self-assembled into irregular meshwork structures. The treatment of the tissue with 10% sodium hydroxide for up to 5 days removed most of these rods and strands, thus exposing a three-dimensional arrangement of collagen fibrils that is often not fully visualized in untreated tissues. With histochemical staining of thinly sectioned tissues using Alcian blue, these rods and strands were positively stained, and thus they were demonstrated to be composed of proteoglycans. The ultrastructural arrangement of the periodontal ligament, observed in this study as a delicate interaction of collagen and proteoglycan components, is likely to play a significant role in the transmission of occlusal forces applied to the tissue and in the dissipation of mechanical shock.

Animals↗

Risks in using siphon-reducing devices in adult patients with normal-pressure hydrocephalus: bench test investigations with Delta valves.

To elucidate the reason for malfunction of Delta valves in patients with normal-pressure hydrocephalus, the authors applied a new concept of the bench test and simulated intracranial pressure (ICP) to measure the resultant flow with a complete shunt system. Subcutaneous pressure on the valve, valve implantation site, and postural hydrostatic differential-pressure changes were simulated in this bench test designed for adult patients with normal-pressure hydrocephalus. Subcutaneous pressure ranged within 6.4 +/- 0.09 cm H2O (mean +/- standard deviation) on the 7th day after the implantation of the valve in rats. A linear correlation between valve closing pressures and the external pressure was observed: gradual increase of the latter resulted in an approximately equal rise in the closing pressure. Closing pressure ranged within the physiological variation of ICP (10 +/- 5 cm H2O) in the supine position. In the erect position it was higher than the physiological variation (+5 to -5 cm H2O) when the valve was placed at the level of the foramen of Monro and lower when placed at the level of the clavicle. This observation indicates that the subcutaneous pressure around the Delta valve significantly affects its closing pressure. An excessive reduction of flow or a functional obstruction occurs when the patient with a Delta valve implanted at the foramen of Monro assumes an erect posture. The authors conclude that Delta valves are not recommended for implantation at the level of the foramen of Monro in patients with normal-pressure hydrocephalus because of the risk of underdrainage. The mastoid process or clavicle may be the alternative levels for its implantation to prevent underdrainage; however, the possibility of shunt malfunction should be kept in mind because subcutaneous pressure is variable among patients and that might affect the performance characteristics of these valves.

Animals↗

[A case of sensitive urethra treated by continent vesicostomy using detrusor tube].

A case of sensitive urethra treated with continent vesicostomy is reported. She suffered from atonic bladder due to a previous pelvic surgery and could not continue clean intermittent self-catheterization because of pain and discomfort, or sensitive urethra. Continent vesicostomy using detrusor tube following Mitrofanoff principle was performed. Postoperatively, the daily life activity improved markedly. Mitrofanoff operation is considered to be applicable to the cases with sensitive urethra after sufficient explanation and consent.

Cystostomy↗

[Superior septal approach for mitral valve surgery].

The superior septal approach (SSA) for mitral valve surgery is a useful approach, but it may bring about demage to sinus node function or an atrial electrical vulnerable condition because the sinus node artery is divided and a large portion of both atria is incised. From April 1992 to December 1994, we used this approach in 17 patients. There was no hospital death and none had perioperative complications associated with the approach. All nine patients in sinus rhythm preoperatively returned to sinus rhythm before discharge from the hospital and remained so at late follow-up. Five of 9 patients with sinus rhythm had electrophysiological examination preoperatively and all 9 patients had the examination postoperatively. Atrial vulnerability was not deteriorated after the operation in all cases. Under pharmacologic autonomic blockade, sinoatrial conduction time (SACT), sinus node recovery time (SNRT) after overdrive atrial pacing, and corrected SNRT were 73 +/- 35 msec, 1142 +/- 168 msec, and 365 +/- 122 msec, respectively. All these values were with in normal range and these were no significant differences between before and after the operation. All patients with sinus rhythm had 3 minutes of Bruce stage 1 exercise 9 months after the operation. The heart rate response to the exercise was as good as in healthy control people. In conclusion, as far as the midterm postoperative period, the effect of SSA on sinus node function and atrial vulnerability was acceptable.

Adult↗

[Autoradiographic study of myocardial fatty acid metabolism in diabetic mouse using 125I-BMIPP].

The existence of diabetic cardiomyopathy has been substantiated in patients with diabetes mellitus. In this study we evaluated two mice with diabetes mellites (DM) and two control mice to determine whether the fatty acid metabolism of the myocardium is abnormal when 125I-BMIPP is used. 125I-BMIPP of 0.74 MBq (20 microCi) was injected, and 30 min later, the mice were slaughtered. Heart, lungs, liver, spleen and kidneys were removed. After freezing the heart, myocardium was sliced into 20 micron sections using a cryostat. Each slice was placed in contact with an imaging plate for autoradiography. A bioimaging analyzer was used to analyze the data. The percent injected dose/g of heart was lower in the DM group than in the control group (11.6 +/- 0.49 vs 18.3 +/- 1.27). Each slice of the DM group also had fewer counts than slices in the control group (p < 0.05 or p < 0.01). These results indicated that fatty acid metabolism in the myocardium was less in the DM group than in the control group.

Animals↗

Structural and calcification patterns of the neonatal line in the enamel of human deciduous teeth.

The neonatal line of the enamel in human deciduous teeth was observed by scanning electron microscopy using secondary and backscattered electron signals. The neonatal line containing irregular structures of enamel prisms with disordered crystal arrangements was basically formed by the abrupt bending of the prisms towards the root. Usually, the prisms gradually bent back again to regain their previous orientation, but the prisms in the inner and the surface layer sometimes ran straight ahead after bending. The prism sheath regions showing hypocalcification contained a relatively large amount of organic material as shown by treatment with chromium sulfate. When etched with ethylenediaminetetraacetic acid (EDTA), such prism sheath regions were extensively eroded due to the lower density of crystals caused by the abrupt bending of the prisms. Abnormally shaped prisms and small prismless areas were occasionally present. The neonatal line formed by the double bending of the prisms is likely to represent a particular type of rhythmic Retzius line rather than a pathologic Retzius line, whereas the hypocalcified sheath regions may be similar to those of some pathologic lines of Retzius.

Child↗

A novel type of retinoic acid receptor antagonist: synthesis and structure-activity relationships of heterocyclic ring-containing benzoic acid derivatives.

A new series of heterocyclic ring-containing benzoic acids was prepared, and the binding affinity and antagonism of its members against all-trans-retinoic acid were evaluated by in vitro assay systems using human promyelocytic leukemia (HL-60) cells. Structure-activity relationships indicated that both an N-substituted pyrrole or pyrazole (1-position) and a hydrophobic region, with these linked by a ring system, were indispensable for effective antagonism. Among the compounds evaluated, optimal antagonism was exhibited by 4-[4,5,7,8,9,10-hexahydro-7,7,10,-10-tetramethyl-1-(3- pyridylmethyl)anthra[1,2-b]pyrrol-3-yl]benzoic acid (31), 4-[4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3-pyridylmethyl)-5- thiaanthral[1,2-b]pyrrol-3-yl]benzoic acid (40), and 4-[4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3- pyridylmethyl)anthra[2,1-d]pyrazol-3-yl]benzoic acid (55), all of which possess a 3-pyridylmethyl group at the five-membered ring nitrogen atom.

Benzoates↗

Unsaturation of the membrane lipids of chloroplasts stabilizes the photosynthetic machinery against low-temperature photoinhibition in transgenic tobacco plants.

Using tobacco plants that had been transformed with the cDNA for glycerol-3-phosphate acyltransferase, we have demonstrated that chilling tolerance is affected by the levels of unsaturated membrane lipids. In the present study, we examined the effects of the transformation of tobacco plants with cDNA for glycerol-3-phosphate acyltransferase from squash on the unsaturation of fatty acids in thylakoid membrane lipids and the response of photosynthesis to various temperatures. Of the four major lipid classes isolated from the thylakoid membranes, phosphatidylglycerol showed the most conspicuous decrease in the level of unsaturation in the transformed plants. The isolated thylakoid membranes from wild-type and transgenic plants did not significantly differ from each other in terms of the sensitivity of photosystem II to high and low temperatures and also to photoinhibition. However, leaves of the transformed plants were more sensitive to photoinhibition than those of wild-type plants. Moreover, the recovery of photosynthesis from photoinhibition in leaves of wild-type plants was faster than that in leaves of the transgenic tobacco plants. These results suggest that unsaturation of fatty acids of phosphatidylglycerol in thylakoid membranes stabilizes the photosynthetic machinery against low-temperature photoinhibition by accelerating the recovery of the photosystem II protein complex.

Acclimatization↗

Arterial-injection chemotherapy for hepatocellular carcinoma using monodispersed poppy-seed oil microdroplets containing fine aqueous vesicles of epirubicin. Initial medical application of a membrane-emulsification technique.

BACKGROUND: Iodized poppy-seed oil (IPSO) has a property of depositing itself selectively in the cells of hepatocellular carcinoma (HCC). A mixture of anticancer agents and IPSO has been used widely because IPSO accumulates in tumors, but its usefulness appears limited because the anticancer agents become separated easily from IPSO and do not remain in the tumor. The authors prepared a long term inseparable, water-in-oil-in-water emulsion (W/O/W) for use in arterial-injection therapy for patients with HCC and evaluated its clinical usefulness. METHODS: The W/O/W was prepared by a membrane-emulsification technique using a controlled pore glass with 10.6-microns pores. From December 1992 to January 1994, the W/O/W containing 8-60 mg of epirubicin was applied to the hepatic arterial-injection therapy for 21 patients with HCC to determine its antitumor and side effects. RESULTS: After arterial infusions with W/O/W, an evident antitumor effect was observed in all 13 patients treated with W/O/W containing 40 mg or more of epirubicin with or without gelatin-sponge particles used simultaneously. In the group treated with the W/O/W containing a high dose (40 mg or more) of epirubicin, even though the gelatin-sponge particles were not used, tumor size was reduced in six of seven patients, and a 50% or greater decrease of initial alpha-fetoprotein (AFP) levels within 14 days was observed in all four patients who showed abnormal levels of serum AFP before treatment. One partial necrosis and two complete necroses of three resected tumors were confirmed histopathologically. Fever (in all patients), nausea (in two), pain in the right upper quadrant of the abdomen (in two), and slight cough (in one) were noted as minor side effects. CONCLUSIONS: To the authors' knowledge, this is the first clinical trial using this emulsion prepared by the membrane-emulsification technique. Emulsification using a fine-pore glass membrane of equal pore size (i.e., controlled-pore glass membrane) is a new technique for preparing lipid microdroplets of equal size (monodispersed) containing aqueous fine microdroplets to form W/O/W: This technique of chemoembolization can be used to treat patients with HCC.

Aged↗

Biochemical analysis of ferritin subunits in sera from adult Still's disease patients.

To determine the origin of the increased serum ferritin that occurs in adult Still's disease (ASD), we analyzed subunits of the serum ferritin as follows. Gel filtration with Sepharose CL-6B demonstrated that the molecular weight of serum ferritin was about 490 kDa. Western blot analysis revealed only L-subunits (molecular weight 19 kDa) in patients with serum ferritin levels higher than 1,000 ng/ml. Patients with serum ferritin levels higher than 1,000 ng/ml, however, showed G-subunits (molecular weight 23 kDa) in addition to the L-subunits. When concanavalin A (Con-A) Sepharose 4B was used in an absorption test, the percentage absorption was extremely low in the patients with serum ferritin levels higher than 1,000 ng/ml. Isoferritin patterns of the patients determined by chromatofocusing revealed traces of acidic ferritin. The findings suggested that glycosylated ferritin does not account for the major portion of the increased serum ferritin.

Adult↗

Role of activation of ornithine decarboxylase and DNA synthesis on ethynylestradiol-induced hepatocarcinogenesis.

We have established an animal model for estrogen-induced hepatocarcinogenesis by oral administration of synthetic hormone to female Wistar rats. Daily treatment of rats with 0.15 mg of ethynylestradiol (EE) for 4 months resulted in the development of hyperplastic foci in all animals. At 12 months of EE treatment, four of the 13 rats (30.8%) developed hepatocellular carcinoma. Ornithine decarboxylase (ODC) activity and DNA synthesis in the liver were activated by a single administration of EE, reaching peak levels at 12 and 48 h respectively. The EE-activated peak levels of both ODC activity and DNA synthesis were markedly elevated at 2 months after consecutive treatment, indicating that the female sex hormone stimulates the cellular proliferation during the initiation phase of carcinogenesis. The activities then gradually decreased, but with the levels higher than those in the controls. On the other hand, simultaneous treatment of rats with tamoxifen completely suppressed the EE-induced ODC activity, hepatic foci formation and hepatocellular carcinoma development. Together with our previous findings of DNA adducts and 8-hydroxydeoxyguanosine formation in the early stage of EE-induced carcinogenesis resulting in DNA damage, the present results suggest that estrogen enhanced ODC activity which was followed by increased DNA synthesis (DNA replication). Moreover, these effects might increase misreading during damaged DNA replication and were closely related to initiation, promotion and progression of hepatocarcinogenesis in this experimental model.

Animals↗

Role of reactive oxygen in synthetic estrogen induction of hepatocellular carcinomas in rats and preventive effect of vitamins.

We have established an experimental model of oral contraceptive-induced hepatocellular carcinomas (HCCs) in female Wistar rats, revealing that ethynylestradiol (EE) and norethindrone acetate have actions as both initiators and promoters. The present time-sequence study was undertaken to clarify the role of free radicals in estrogen induction of HCC by measuring detoxifying enzyme activities and levels of 8-hydroxydeoxyguanosine (8-OH-dG) and by assessing the effects of concomitant vitamin C, vitamin E or beta-carotene administration on hepatocarcinogenesis. During 12 months oral administration of EE (0.075 or 0.75 mg/day), the 8-OH-dG levels reached peak values after 1 month, when they were significantly elevated as compared with the controls. Glutathione peroxidase demonstrated a tendency to decrease. Histologically, pre-neoplastic lesions assessed by immunohistochemical staining for placental glutathione S-transferase (GST-P) were first observed at 2 months in the groups given 0.075 and 0.75 mg/day of EE alone, with incidences of HCC at 12 months being 8.7% and 38.5% respectively. Combined administration of vitamins with 0.075 mg EE/day reduced the elevation of the 8-OH-dG levels. GST-P-positive lesions were first observed at 4 months in the vitamin E group and at 6 months in the vitamin C and beta-carotene groups. As compared with the value in the 0.075 mg EE alone group, vitamin administration significantly reduced the numbers of GST-P-positive foci after 12 months of treatment. The incidences of HCC at 12 months were 0% in the vitamin C group, 4.5% in the vitamin E group and 4.8% in the beta-carotene group, i.e. administration of the vitamins inhibited the development of GST-P-positive foci, with suppression of HCC. The results thus suggest that free radicals play an important role in the induction of HCC by estrogen.

8-Hydroxy-2'-Deoxyguanosine↗

Basic fibroblast growth factor may repair experimental cerebral aneurysms in rats.

BACKGROUND AND PURPOSE: To determine whether basic fibroblast growth factor (FGF) can induce proliferative response of endothelial cells and/or smooth muscle cells in aneurysmal lesions, we investigated the effect of the intravenous administration of basic FGF on experimental cerebral aneurysms. METHODS: Cerebral aneurysms were induced in rats by ligation of the unilateral common carotid artery, producing hypertension. Three months later, basic FGF was intravenously injected in two groups of randomly divided rats on days 1, 3, and 5 at two different doses (low dose: 2 micrograms/100 g body wt per day; high dose: 5 micrograms/100 g body wt per day). In a control group, normal saline was similarly injected. The junctions of the anterior cerebral artery (ACA) and the olfactory artery (OA) were examined with a light microscope. Aneurysmal changes were defined as the lesions with discontinuity of the internal elastic lamina in more than half of the outward dilated wall. Depending on whether the smooth muscle cell layer was present in the whole wall, the lesions were divided into two stages: early aneurysmal lesion (whole area) and saccular aneurysm (not totally preserved). RESULTS: The control and the low-dose groups presented no obvious intimal thickening in the intact ACA-OA junctions of both nonligated and ligated sides as well as in the aneurysmal changes. In contrast, in the high-dose group, various degrees of intimal thickening in the wall were detected in 7 of 15 early aneurysmal lesions (P = .019, Fisher's exact test). Immunohistochemistry showed the proliferated cells to be smooth muscle cells. CONCLUSIONS: These results demonstrate that exogenous basic FGF induces the proliferative response of smooth muscle cells in aneurysmal lesions in rats.

Animals↗