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Biomedical subjects

K Ishihara

Publications and source records attributed to K Ishihara.

At least 307 records · Page 17Linked to original sources
PubMed1996

Pancreatic islet cells express BST-1, a CD38-like surface molecule having ADP-ribosyl cyclase activity.

Cyclic ADP-ribose (cADPR), a well-known stimulator of ca(2+) release from the intracellular Ca(2+) pool, has recently emerged as a potential regulator of insulin secretion in pancreatic beta cells. As recently described, BST-1 is a glycosyl-phosphatidylinositol (GPI)-anchored surface molecule that exhibits homology with CD38 and Aplysia ADP-ribosyl cyclase. Like CD38, BST-1 has both ADP-ribosyl cyclase and cADPR hydrolase activities. As a step toward elucidating the physiological role of cADPR in insulin secretion we examined whether BST-1 is expressed in pancreatic islet cells. Sensitive reverse transcription-polymerase chain reaction detected almost as abundant expression of BST-1 mRNA in pancreatic islets as CD38 mRNA. Immunohistochemical analyses utilizing mirror image sections revealed that BST-1 protein is expressed in a majority of the cells in pancreatic islets and that at least beta cells and, to an even greater extent, alpha cells express BST-1. These observations suggest the involvement of multiple enzymes in the regulation of cADPR concentrations in pancreatic islet cells.

ADP-ribosyl Cyclase↗
PubMed1996

Stimulation of mucin biosynthesis in rat gastric mucosa by FRG-8813 and its structural analogs.

Certain chemical properties, which may determine the stimulatory actions of the new histamine H2 receptor antagonist, FRG-8813 (2-(furfurylsulfinyl)-N-(4-[4-(piperidinomethyl)-2-pyridyl]o xy-(Z)- 2-butenyl)acetamide), on mucin biosynthesis, were identified by considering the derivation of this drug using an organ culture system of the rat stomach. [3H]Glucosamine and [35S]sulfate incorporation was stimulated in the corpus region by FRG-8813 and its structural analog, compound A (N-[4-[[4- (piperidinylmethyl)pyridyl]-2-oxy]-(Z)-2-butenyl]phthalimide). The chronotropic response to histamine in the guinea pig right atria was suppressed by FRG-8813 in a concentration-dependent fashion. In contrast, compound A did not suppress the histamine-induced response. Ranitidine at 10(-4) M did not suppress the FRG-8813-induced increase in [3H]glucosamine incorporation into mucin. These results suggest that the pyridine derivative and amide structure are chemically important in FRG-8813 as a stimulant on mucus metabolism. Also, this effect is not directly due to histamine H2 receptor antagonism.

Acetamides↗
PubMed1996

Allografting intervertebral discs in dogs: a possible clinical application.

STUDY DESIGN: A lumbar disc is a tissue that is often a cause of low back pain. We conducted experimental allografting of intervertebral discs in dogs. OBJECTIVES: To evaluate the clinical potential for allografting of intervertebral disc. SUMMARY OF BACKGROUND DATA: There have been few reports on the allografting of intervertebral discs. The allografting of discs frozen at -196 C has never been documented. In the present experiments, we studied the effect of freezing at -80 C and -196 C on disc allografts to 25 hybrid adult dogs. METHODS: A vertebral disc was obtained from donor dogs with parts of the adjoining vertebral bodies to serve as the allograft disc unit. After soaking in 10% dimethyl sulfoxide at 4 C, the allograft discs were frozen and stored at either -80 C or -196 C. After storage for approximately 4 weeks, they were transplanted peritoneally into the recipient lumbar vertebrae and fixed using plates and screws to preserve mobility of the grafted disc. At the same time, cells from allograft discs were incubated to examine their ability to synthesize proteoglycan and collagen. Radiologic examination of the changes after surgery in the intervertebral space was followed serially. RESULTS: Radiographs revealed a complete bone union of the vertebral bodies at 5 months and gradual narrowing of the intervertebral space beginning at 6 months. Histologically, the anulus fibrosus was well preserved, especially in disc units stored at -196 C. Cellular synthetic activity was seriously diminished. CONCLUSIONS: Our results indicate that allograft of intervertebral discs has clinical potential because it can serve as a dynamic disc spacer for a certain period of time, but its long-term merits and demerits have to be established.

Animals↗
PubMed1996

Ectopic induction of cartilage and bone by bovine bone morphogenetic protein using a biodegradable polymeric reservoir.

Two kinds of bone morphogenetic protein (BMP) containing polymeric reservoirs made from poly(lactide-co-glycolide) (PLG) and a mixture of PLG/poly(ethylene glycol) (PEG) (PLG/PEG) were implanted into mice femoral muscles. In the PLG/PEG reservoir with BMP, bone formation was induced within 3 weeks. On the other hand, in the PLG reservoir with BMP scarcely any bone formation could be observed. The results suggest that the carrier system is most important for the development of BMP-induced bone formation and the PLG/PEG reservoir system is available for BMP delivery.

Animals↗
PubMed1996

Improved blood compatibility of segmented polyurethanes by polymeric additives having phospholipid polar groups. I. Molecular design of polymeric additives and their functions.

To improve the blood compatibility of a segmented polyurethane (SPU), 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer was blended with the SPU. The MPC was copolymerized with cyclohexyl methacrylate (CHMA) or 2-ethylhexyl methacrylate (EHMA), and the MPC polymers obtained could be dissolved in the same solvent as the SPU (Tecoflex 60). The blended membranes composed of SPU and MPC polymers were prepared by a solvent evaporation method. A small amount of MPC polymer in the blended membrane leached out after immersion in water for 10 days. The X-ray photo electron spectra indicated that the MPC moieties were located at the surface of the SPU membrane blended with poly(MPC-co-CHMA). On the other hand, the poly-(MPC-co-EHMA) was located homogeneously in the SPU membrane. The mechanical properties of the SPU membrane, as determined by tensile stress-strain measurements, changed very little even after addition of the MPC polymers. Blood compatibility of the blended membrane was evaluated by blood-cell adhesion on the surface when the membranes were placed in contact with rabbit whole blood or platelet-rich plasma. The addition of MPC polymer in the SPU membrane dramatically reduced cell adhesion. It is concluded that the blending of the MPC polymer in the SPU membrane is an effective method for imparting nonthrombogenicity.

Animals↗
PubMed1996

Improved blood compatibility of segmented polyurethane by polymeric additives having phospholipid polar group. II. Dispersion state of the polymeric additive and protein adsorption on the surface.

To improve the blood compatibility of a segmented polyurethane (SPU), phospholipid polymer, i.e., 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymerized with cyclohexyl methacrylate or 2-ethylhexyl methacrylate, was blended into SPU as a polymeric additive. The blending was achieved by a solvent-evaporation technique from a homogeneous solution containing both the SPU and the MPC polymer. Surface analysis of the SPU membrane blended with the MPC polymer (SPU/MPC polymer membrane) revealed that the MPC polymer was concentrated at the surface of the SPU membrane which contacted the substrate, Teflon, compared with that which contacted air during the membrane-formation period. The dispersion state of the MPC polymer in the SPU membrane was evaluated in detail by staining the MPC unit with osmium tetraoxide. When sonication was applied during preparation of the mixed solution containing SPU and the MPC polymer, the dispersion of the MPC polymer in the SPU membrane was different from that without sonication. That is, the size of the domains of the MPC polymer became smaller but the number of the domains increased. The amount of the MPC polymer mixed with SPU affected the dispersion state. Plasma proteins adsorbed on the SPU/MPC polymer membrane surface after contact with human plasma were detected by gold-colloid-labeled immunoassay. Both albumin and fibrinogen were observed on the SPU membrane; however, the amount of these proteins was reduced on the SPU/MPC polymer membrane. Thus it was concluded that the blood compatibility of the SPU was effectively improved by the blending of the MPC polymer.

Adsorption↗
PubMed1996

Bone morphogenetic protein encapsulated with a biodegradable and biocompatible polymer.

To develop a controlled release system for bone morphogenetic protein (BMP), poly(DL-lactide-co-glycolide) (PLGA) capsules containing BMP were prepared by an interfacial precipitation method using a water-in-oil-in-water emulsion. The surface morphology, particle size distribution, and hydrolytic degradation rate of the PLGA capsules were examined. The encapsulation yield and release rate of BMP in vitro were measured using fluorescein isothiocyanate-labeled BMP. The amount of BMP released from PLGA capsules increased between days 3 and 5. In addition, the effectiveness of BMP encapsulated in PLGA to induce bone formation in vivo was also examined by subcutaneous implantation in rats. Complete digestion of the capsules and new bone formation including bone marrow were identified by histologic examination of harvested tissues at 3 weeks after implantation. These results demonstrated that encapsulation of BMP with PLGA could be a promising method to induce bone in clinics.

Animals↗
PubMed1996

Elevated levels of the soluble form of bone marrow stromal cell antigen 1 in the sera of patients with severe rheumatoid arthritis.

OBJECTIVE: Bone marrow stromal cell antigen 1 (BST-1) is a novel glycosyl phosphatidylinositol-anchored ectoenzyme, which is overexpressed on bone marrow stromal and synovial cell lines derived from patients with rheumatoid arthritis (RA). To investigate the pathophysiologic roles of BST-1 in RA, we established an enzyme-linked immunosorbent assay (ELISA) system to detect the soluble form of BST-1 (sBST-1) and examined levels of sBST-1 in the sera of RA patients. METHODS: Concentrations of sBST-1 in sera from healthy donors and from patients with RA, osteoarthritis, Sjögren's syndrome, and systemic lupus erythematosus were measured with the ELISA. RESULTS: In 7% of the RA patient samples (10 of 143), concentrations of serum sBST-1 were higher (approximately 30-50-fold) than in non-RA samples. Serum sBST-1 concentrations showed no correlation with age, C-reactive protein level, or rheumatoid factor level. All RA patients with high concentrations of serum sBST-1 had severe disease with involvement of several large joints. CONCLUSION: We believe the measurement of serum sBST-1 may have prognostic value, but further analysis is necessary to clarify the clinical significance of elevated sBST-1 in RA.

ADP-ribosyl Cyclase↗
PubMed1996

Establishment of monoclonal antibodies against carbohydrate moiety of gastric mucins distributed in the different sites and layers of rat gastric mucosa.

Eight monoclonal antibodies (MAbs), designated RGM21 approximately RGM42, were generated against mucin purified from the rat gastric mucosa. By applying ELISA, all of these MAbs were proved to react not only with the purified mucin, but also with the oligosaccharide mixture obtained from the antigenic mucin by alkaline borohydride treatment. Treatment of the mucin-attached ELISA well with trypsin, sodium periodate or galactose oxidase prior to the addition of the MAb was applied to characterize these MAbs. Histochemical observation indicated that all these MAbs were able to stain the formalin fixed-paraffin embedded sections of the rat gastroduodenal mucosa. Although each of these MAbs reacted with distinct mucus-producing cells localized in particular regions of the gastroduodenal mucosa, their staining specificity could generally be classified into four groups. These MAbs might be useful for estimating the physiological and pathological changes of mucins in the gastric mucosa.

Animals↗
PubMed1996

Topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of spontaneously epileptic rats (SER).

The spontaneously epileptic rat (SER), a double mutant, manifests both tonic and absence-like seizures. The effect of topiramate, a novel antiepileptic drug, on the extracellular levels of excitatory amino acids (EAA) in the hippocampus of SER was investigated using in vivo microdialysis. The basal levels of glutamate and aspartate in dialysates of hippocampus in SER were 2- to 3-fold higher than those in normal Wistar rats. Both the dose-response relationship and the time course of the suppression of tonic seizures by topiramate were similar to the attenuation of glutamate level in SER. Topiramate (40 mg/kg i.p.) significantly (P < 0.05) reduced both glutamate and aspartate levels in SER while showing no effect on normal Wistar rats. These findings suggest that topiramate reduces abnormally high extracellular levels of glutamate and aspartate in the hippocampus of SER. This effect may, at least in part, be related to the anticonvulsant activity of topiramate.

Animals↗
PubMed1996

Effects of a newly developed transdermal clonidine delivery system (M-5041T) on EEG sleep-wake cycle in relation to plasma concentration in rabbits.

1. The effects of a transdermal clonidine delivery system (M-5041T) on EEG sleep pattern with relation to plasma concentrations in unrestrained rabbits were investigated and compared with those of intravenous (i.v.) administration of clonidine. 2. Although M-5041T did not affect the EEG recorded from cortex and hippocampus at doses up to 2.5 mg/kg, slow theta waves in hippocampal EEG accompanied by low-voltage slow waves in cortex were induced at a higher dose of 12.5 mg/kg. On i.v. injection (0.25 mg/kg), EEG tracings with bursts of high-voltage slow waves in cortical EEG and slow theta waves in hippocampus were observed. 3. At doses of 0.5 and 2.5 mg/kg, M-5041T did not cause any alterations of the sleep-wake cycle, and plasma concentrations of 1-2 ng/ml were maintained for an 8-hr observation period. However, this delivery system significantly suppressed the incidence of rapid-eye movement sleep (REMS) from 11.9 to 4.7% and enhanced drowsiness (DW) from 9.0 to 21.0% during the 8-hr recording period at 12.5 mg/kg with a plasma concentration of up to 10 ng/ml. Contrary to transdermal administration, i.v. clonidine (0.25 mg/kg) completely blocked light and deep slow wave sleep as well as REMS with a plasma concentration indicated more than 10 ng/ml at 2 hr post administration. Recovery to a normal sleep-wake cycle was eventually established thereafter. The incidence of REMS and DW were significantly decreased from 11.9 to 6.3% and increased from 9.0 to 25.5%, respectively. 4. Concurrent monitoring of clonidine concentrations in cerebrospinal fluid (CSF) indicated that CSF concentrations after patching M-5041T, as well as i.v. clonidine, were almost equal to plasma levels. 5. These results suggest that alteration of the sleep-wake cycle with clonidine occurs depending upon brain concentrations, which increase to a level similar to that in plasma after administration, and that M-5041T at doses of less than 2.5 mg/kg could establish effective hypertensive therapy without obvious effects on the cycle.

Animals↗
PubMed1996

Effects of traditional herbal medicine on gastric mucin against ethanol-induced gastric injury in rats.

The effect of the traditional herbal medicine, Rikkunshi-to and its component crude drugs, Zingiberis Rhizoma and Glycyrrhizae Radix, on the gastric mucin was studied using a method developed to separate and quantify the mucin localized in the different layers of rat gastric mucosa. The oral administration of spray-dried extract to Rikkunshi-to (1000 mg/kg), Zingiberis Rhizoma (500 mg/kg) and Glycyrrhizae Radix (500 mg/kg) significantly prevented gastric mucosal damage induced by 70% ethanol in rats. In ethanol-treated rats the mucin content of the deep mucosa was reduced, and the reduction of the deep corpus mucin content was significantly inhibited by pretreatment of Rikkunshi-to and Zingiberis Rhizoma. Rikkunshi-to and Glycyrrhizae Radix pretreatment increased the surface mucin content by 140 and 146%, respectively. The effect on the gastric mucin by each drug differed in the different layers of the gastric mucosa.

Administration, Oral↗
PubMed1996

Development of a haemocompatible pO2 sensor with phospholipid-based copolymer membrane.

This paper describes research to improve the haemocompatibility of an intravascular pO2 sensor utilizing a novel copolymer membrane. This material is based on a methacrylate monomer having an electrically neutral head group, 2-methacryloyloxyethyl phosphorylcholine (MPC), copolymerized with n-butyl methacrylate (BMA). The MPC mimics the outer layer lipid structure of the red blood cell membrane, and thus poly (MPC-co-BMA) could be expected to show excellent compatibility with blood. In this paper the methods of preparation of a pO2 sensor covered with different types of membrane, including polyetherurethane (PU), polyvinyl chloride (PVC), poly (MPC-co-BMA) and a compound membrane [PVC+poly (MPC-co-BMA)] are described. The surface chemical structure of the different types of membrane were characterized with Fourier transform infrared spectroscopy. Scanning electron microscopy was used to examine the surface contamination after the sensors had been used in blood. The properties of the sensors were first assessed in phosphate-buffered solution, and the short-term and long-term performances were then demonstrated by use of buffer with mixed proteins, serum and whole human blood. The sensors coated with poly (MPC-co-BMA) and PVC+poly (MPC-co-BMA) membranes showed stable behaviour in static human blood, whereas the sensors with PU and PVC membrane were subject to a continuous signal deterioration during the test period.

Biocompatible Materials↗
PubMed1996

Nonobstructing accessory mitral valve tissue and ventricular septal defect.

A 4-month-old boy with ventricular septal defect was found to have accessory mitral valve tissue attached to the anterior leaflet of the mitral valve. Operation was successfully performed to excise the accessory mitral tissue in the left ventricular outflow tract and close the ventricular septal defect. Most previously reported cases with accessory mitral valve tissue were associated with left ventricular outflow tract obstruction. This boy had no pressure gradient across the left ventricular outflow tract. The indications for prophylactic excision of nonobstructing accessory mitral valve tissue in a patient with other forms of congenital cardiac disease are discussed.

Heart Septal Defects, Ventricular↗
PubMed1996

The origin and significance of spinal cord pulsation.

We studied the origin and mechanism of spinal cord pulsation in ten dogs in order to elucidate its clinical significance. Under general anesthesia, a 6 cm length of the animals' cervical spinal cord was exposed and the cerebrospinal fluid removed. The amplitude of spinal pulsation was then measured by means of ultrasonography in Mode M. The measurements were made after the spinal cord was cut: (1) on the cranial side; (2) on the cranial as well as caudal side, with the nerve roots and radicular arteries intact; (3) on both sides as in (2), which was then supplemented with the severance of the nerve roots and radicular arteries. It was demonstrated that, while the pulsation amplitude stood at an average of 88.0 microns before the surgical treatment, it rose to 455.0 microns in (1) and 274.8 microns in (2), but dropped to nearly zero in (3). The 5.2-fold increase in pulsation following the cordotomy on the cranial side was attributed to two factors: (1) the increased spinal mobility due to the cordotomy; (2) the elevation of blood pressure. The results of the three different degrees of spinal detachment suggested that spinal pulsation derived mainly from the radicular arteries and that its presence indicated low tonicity in the spinal cord and favorable circulation in the radicular arteries.

Animals↗
PubMed1996

Stage-specific expression of mouse BST-1/BP-3 on the early B and T cell progenitors prior to gene rearrangement of antigen receptor.

Human bone marrow stromal cell antigen 1 (BST-1) was identified as a glycosylphosphatidyl-inositol-anchored ectoenzyme expressed on bone marrow stromal or synovial cell lines and having the ability to facilitate pre-B cell line growth. The analysis of the expression of mouse BST-1/BP-3 on the surface of lymphoid cells in the bone marrow and thymus revealed that it was very transiently expressed on both B and T cell progenitors undergoing gene rearrangement of the antigen receptor. Among CD45R+ CD43+ B cell progenitors in the bone marrow, BST-1 expression appeared on the CD24 (heat stable antigen)+, CD19+ or CD117 (c-kit)+ population. In the thymus, BST-1 was expressed on CD4-CD8-CD3- [triple negative (TN)] CD90 (Thy-1)+ cells. In TN thymocytes, the majority of CD25+ cells and CD44(10)/- cells expressed BST-1. In fetuses, BST-1+ cells appeared in the thymus and liver at day 14 and 16 of gestation respectively. The expression level of BST-1 by fetal thymus was maximal and > 60% of thymocytes were positive for BST-1 at day 15 or 16 and the proportion then gradually decreased during development. Among day 15 fetal thymocytes, BST-1 was negative on the CD44+ CD25- fraction, very slightly positive on the CD44+ CD25+ fraction, and strongly positive on the CD44(10)/- CD25+ and CD44-CD25- fractions. These results showed that murine BST-1 is a useful marker for lymphoid progenitor cells initiating gene rearrangement of their antigen receptors.

ADP-ribosyl Cyclase↗
PubMed1996

Clinical and pathological features of cutaneous malignant melanoma: a retrospective analysis of 124 Japanese patients.

A review of mainly histopathologic factors associated with the survival of patients with malignant melanoma was carried out in a retrospective study of 124 Japanese patients treated at the National Cancer Center Hospital between July 1962 and December 1992. There were 60 females and 64 males, and the median follow-up period was 52.7 months (range, 1.1 to 235.3 months). The histologic features included tumor thickness, level of invasion, histologic subtype, ulceration, pigmentation, and cell type. Melanomas thicker than 1.5 mm (P<0.01) and with ulceration (P<0.001) had a significantly worse prognosis. With regard to histologic type, ten-year survival was 65.1% for acral lentiginous melanoma, 50.7% for nodular melanoma, and 47.0% for superficial spreading melanoma (SSM), there being no significant differences among them. We suggest that the prognosis was affected not by histologic type but by the large radial or vertical growth component. With regard to clinical features, the clinicopathological stage, patient age, and year when the disease was diagnosed were reflected in the prognosis (P<0.001). Multifactorial analysis showed that the most significant prognostic variables were histopathologic type (SSM or other), stage (I and II or III and IV), and patient age (<70 or > or = 70 yr).

Adolescent↗