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Biomedical subjects

M Nishijima

Publications and source records attributed to M Nishijima.

At least 145 records · Page 8Linked to original sources

CD14 is a pattern recognition receptor.

Septic shock caused by a diverse group of bacterial pathogens is a serious human disease. Recognition of bacterial envelope constituents is one mechanism used by mammalian cells to initiate responses leading to bacterial killing or, unfortunately, responses that also cause fatal septic shock. Here we show that CD14 plays a key role in initiating cell activation by a group of bacterial envelope components from Gram-negative and Gram-positive microorganisms, as well as mycobacteria. We propose that CD14 is a receptor used by mammalian cells to recognize and signal responses to a diverse array of bacterial constituents. This finding defines the molecular basis for innate microbial immunity; implicit in these findings are new possibilities for therapeutics.

Animals↗

Identification of a biochemical lesion, and characteristic response to lipopolysaccharide (LPS) of a cultured macrophage-like cell mutant with defective LPS-binding.

We have previously isolated a lipopolysaccharide (LPS)-resistant mutant (named LR-9) of a cultured macrophage-like cell line, J774.1. This mutant had defective LPS binding [Hara-Kuge, S., Amano, F., Nishijima, M., and Akamatsu, Y. (1990) J. Biol. Chem. 265, 6606-6610]. In this study, we found that: (1) LPS-binding to parental J774.1 cells was dependent on a serum factor with a molecular weight of about 60 kDa, probably LPS binding protein (LBP); (2) LPS-binding to J774.1 cells was markedly reduced by treating the cells with phosphatidylinositol-specific phospholipase C (PI-PLC); (3) mutant LR-9 cells were defective in LPS-binding even in the presence of serum; (4) LR-9 cells lacked CD14 protein on flow cytometric and immunoblot analyses, but retained normal CD14 mRNA levels on RNA blot analysis; (5) small amounts of LPS (1 to 10 ng/ml) activated J774.1, but not LR-9 cells, to secrete tumor necrosis factor-alpha and to release arachidonate metabolites, whereas both J774.1 and LR-9 were activated by large concentrations of LPS (100 to 1,000 ng/ml). These results provide genetic evidence that CD14 molecules in J774.1 cells play a crucial role in LPS-binding and in LPS-triggered signal transduction, and indicate that large amounts of LPS can activate J774.1 cells without the participation of CD14 molecules.

Acute-Phase Proteins↗

Growth requirements of hyperthermophilic sulfur-dependent heterotrophic archaea isolated from a shallow submarine geothermal system with reference to their essential amino acids.

Three hyperthermophilic sulfur-dependent heterotrophs were isolated from a shallow submarine hydrothermal system at an inlet of Kodakara-jima island, Kagoshima, Japan. The isolates grew at 60 to 97 degrees C, with the optimum temperatures at 85 to 90 degrees C. Sensitivity to rifampin and the existence of ether lipids indicated that the isolates are hyperthermophilic archaea. Partial sequencing of the genes coding for 16S rRNA showed that the three isolates are closely related to the genus Thermococcus. They grew on proteinaceous mixtures, such as yeast extract, Casamino Acids, and purified proteins (e.g., casein and gelatin), but not on carbohydrates or organic acids as sole carbon and energy sources. Nine amino acids were essential for growth of isolate KS-1 (Thr, Leu, Ile, Val, Met, Phe, His, Tyr, and Arg). Isolate KS-2 required Lys in addition to the nine amino acids, and KS-8 required Lys instead of Tyr. In comparative studies, it was shown that Thermococcus celer DSM 2476 required 10 amino acids (Thr, Leu, Ile, Val, Met, Phe, Tyr, Trp, Lys, and Arg) while Pyrococcus furiosus DSM 3638 required only Ile and Val. The hyperthermophilic fermentative eubacterium Thermotoga neapolitana DSM 4359 did not require any amino acids for growth.

Amino Acids, Essential↗

An experimental model of symptomatic vasospasm induced by oxyhemoglobin in rabbits.

BACKGROUND AND PURPOSE: There are many experimental models for studies of cerebral vasospasm. However, no ideal model has been established thus far to comparatively reproduce the ischemic state of the brain that may occur in patients after subarachnoid hemorrhage. METHODS: In the present study, we attempted to induce severe vasospasm in rabbits by using an oxyhemoglobin-rich blood product prepared from hemolyzed arterial blood and evaluate neurological symptoms, cerebral angiogram, cerebral blood flow, and histology. RESULTS: Clinically significant neurological symptoms were observed in about half of the rabbits. There was no significant correlation between angiographic results of the vasospastic state of the main artery and the severity of neurological symptoms observed. However, the cerebral blood flow was significantly lower than in the control group and significantly correlated with the severity of neurological symptoms. On histological examination, lesions were found in about half of the rabbits. Development of obvious infarction was found more frequently than in other reported models. CONCLUSIONS: These results suggest that this model is appropriate as an experimental model of vasospasm occurring after subarachnoid hemorrhage and is especially useful in that it induces vasospasm intense enough to cause obvious infarction.

Animals↗

Biological activity and structural characterization of alkaline-soluble polysaccharides from the kernels of Prunus mume Sieb. et Zacc.

The fruits of Prunus mume Sieb. et Zacc. (Japanese name, ume) have been used as a traditional drug and health food. In order to study the active components of P. mume, the polysaccharide fractions were extracted with cold water, hot water and aqueous sodium hydroxide from the kernels of P. mume. We found that some of the polysaccharide fractions exhibited various types of biological activities such as mitogenesis, activation of the alternative pathway of complement and activation of clot formation in human plasma. A polysaccharide, P-1, obtained from the cold 0.5 M NaOH extract was purified by ion-exchange chromatography and gel-filtration, P-1 contained 62.0% neutral sugar as glucose and 38.4% uronic acid (as galacturonic acid), and was free from protein. The neutral sugars of P-1 were arabinose, xylose, rhamnose and galactose in a molar ratio of 9.4:3.4:1.1:1.0, following analysis by gas-liquid chromatography. In addition, galacturonic acid was identified by thin-layer chromatography. The molecular weight of P-1 was found to be more than 2,000,000 by gel-filtration on Toyopearl HW 65F. P-1 showed mitogenic activity towards spleen cells of both C3H/HeN and C3H/HeJ, suggesting that it was free from bacterial endotoxic lipopolysaccharides.

Animals↗

Ischemic brain damage induced by repeated brief occlusions of bilateral common carotid artery in rats.

Two temporary occlusions of the bilateral common carotid artery for 15 min with an interval of 15 min induced severe brain tissue damage in normotensive Wistar rats. Although no lesions were seen after a single 15-min occlusion, severe ischemic lesions were found in 68% (49/72) of the rats injected to two consecutive occlusions for 15 min with an interval of 15 min, and the incidence was significantly higher than that in the rats subjected to a single 30-min occlusion (32%, 6/19) or two 15-min occlusions with an interval of 30 min (11%, 1/9). The local cerebral blood flow (lCBF) in the caudoputamen, however, was decreased by only 40-60% of pre-occlusion level during occlusions. These results suggest that intermittent incomplete disruption of CBF with short intervals could be more hazardous than a continuous interruption of the same duration.

Animals↗

Analysis of plasma and hematoma lipids related to choline glycerophospholipid in patients with chronic subdural hematoma.

The levels of platelet-activating factor (PAF) and lipid metabolites related to choline glycerophospholipid were measured in the plasma and hematoma samples obtained from patients with chronic subdural hematoma. The ratio of lyso-choline glycerophospholipids (lysoPC) to choline glycerophospholipids (PC) in hematoma correlated with the interval between the onset of symptoms and surgery. PC and lysoPC fatty acyl moieties in plasma and hematoma were essentially similar. These results suggest that the lysoPC to PC ratio in hematoma can determine the age of the chronic subdural hematoma, and that the origin of hematoma may be circulating blood. The levels of PAF in the plasma of chronic subdural hematoma patients were significantly greater than in healthy volunteers. PAF may be involved in the enlargement of chronic subdural hematoma.

Aged↗

Multiple cerebral vascular malformations and spontaneous regression--case report.

A female infant manifested a rare case of spontaneous regression of a vascular malformation in the occipital lobe after removal of another arteriovenous malformation in the frontal lobe. She was born with multiple nevi on the face, body, and upper and lower extremities. She demonstrated developmental retardation at 8 months of age. Computed tomography at 11 months of age demonstrated ventricular enlargement and a mass in the subdural portion of the left anterior fossa. Magnetic resonance images demonstrated signal void signs in the left frontal lobe, which suggested vascular malformation. Cerebral angiograms disclosed two vascular malformations. The malformation in the frontal lobe was totally removed. Cerebral angiograms 25 days after the operation failed to demonstrate either vascular malformation previously observed. Hemodynamic change following the removal of the arteriovenous malformation may have contributed to the occlusion of the remaining malformation.

Cerebral Angiography↗

Radiation exposure in endovascular surgery of the head and neck.

PURPOSE: To evaluate the radiation risk to the operator and the patient during endovascular surgery of the head and neck. METHODS: The dose was measured using thermoluminescence dosimeters attached at the body surface of the operator and the patient during 15 endovascular surgeries (3 for arteriovenous malformation, 8 for dural arteriovenous fistulas, and 4 for other disorders of the head and neck). The dose was measured at seven sites on the operator and at five sites on the patient. RESULTS: The mean number of digital subtraction angiography studies and fluoroscopy time were 21 +/- 10 and 73 +/- 24 minutes, respectively. The equivalent dose range at each site in the operator was 0.12 to 0.88 mSv (glabella), 0.06 to 1.1 and 0 to 0.09 mSv (neck, outside and inside the protector, respectively), 0 to 0.20 mSv (left should, inside the protector), 0.09 to 1.99 mSv (left arm), 0.05 to 3.55 mSv (left hand), and 0 to 0.49 mSv (pubis, inside the protector). Those in the patients were 3.1 to 136 mSv (glabella), 13 to 5441 mSv (right temporal area), 4 to 186 mSv (left temporal area), 0.1 to 51 mSv (neck), and 0 to 0.62 mSv (pubis). CONCLUSIONS: The total doses at the operator's eyes and left hand during the course of a year may exceed the dose limits recommended by the International Commission on Radiological Protection. Operators should wear not only body protectors, but also thyroid protectors and lead glass spectacles. The equivalent dose at the right temporal area of the patient may exceed the deterministic dose for transient erythema or alopecia of the skin even in one endovascular procedure.

Adolescent↗

[A clinical study on the complications associated with laser therapy for cervical neoplasia].

Six hundred and fifty-nine patients with cervical neoplasia were treated by either vaporization (395 patients) or excisional conization (264 patients) with various Lasers. The complications associated with the therapies were examined with reference to the Laser sources and in the local anesthesia and non anesthesia groups. Six hundred and thirty-nine patients were treated on an outpatient basis without local anesthesia (37.7%) or with local anesthesia (62.3%). During the procedures, the patients complained of pain and a hot sensation in the lower abdomen in 64.6% in the vaporization (vapor) group and 60.7% in the conization (cone) group. In the local anesthesia group, 2.9% of the vapor and 4.0% of cone group complained of nothing. Uncontrollable bleeding during the procedures was most common in 12.8% and 32.3% in the CO2 vapor and cone groups, respectively. Misirradiation of the vaginal wall and vulva occurred in 3.3% in all vapor groups. On the other hand, the incidence of burns to both areas in all cone groups was 7.2%. The patients who were given an analgesic were 1.3% in all vapor groups and 2.5% in all cone groups. Delayed bleeding in those who received some treatment to stop it occurred in 14.7% in all vapor groups and also in 11.0% in all cone groups. Cervical stenosis was seen in 3.8% in all vapor groups and in 8.6% in all cone groups. No infection of the lasered site was observed in the vapor groups, but was observed in 0.8% in the cone groups. The culture test showed both E. coli positive.

Abdominal Pain↗

[Circulatory effects of stellate ganglion block in idiopathic facial palsy].

The circulatory effects of stellate ganglion block (SGB) on the blood flow through the common carotid artery were determined in 35 patients in acute phase of idiopathic facial palsy (Bell's palsy). SGB was performed by para-tracheal approach with 8 ml of 1% mepivacaine. The blood flow was measured with an ultrasonic blood flowmeter before and 30 minutes after SGB at both sides of the common carotid artery in 20 cases. Measurement was performed continuously for 90 minutes on the palsy side in the other 15 patients. Before SGB, there were no significant differences between the blood flow of the palsy side and the intact side. Thirty minutes after SGB, the blood flow markedly increased to 169.4 +/- 6.2% on the performed side with no change on the non-performed side in 20 cases. In the other 15 patients, the blood flow increased significantly 5 minutes after SGB and reached its peak of 179.7 +/- 11.1% at 20 minutes later. This increase continued for 75 minutes after SGB. It is well known that impaired microcirculation in the facial nerve has an important role in the pathophysiology of Bell's palsy. In view of the fact that the nutrient arteries for the facial nerve are the peripheral branches of the external carotid artery, we believe that SGB which causes significant increase in the blood flow through the common carotid artery is an effective treatment in Bell's palsy.

Adolescent↗

A somatic cell mutant defective in phosphatidylglycerophosphate synthase, with impaired phosphatidylglycerol and cardiolipin biosynthesis.

Phosphatidylglycerophosphate (PGP) synthase catalyzes a reaction involved in the synthesis of phosphatidylglycerol (PG), which serves as a metabolic precursor for cardiolipin (CL), found primarily in the mitochondrial membranes of eukaryotic cells. We isolated a Chinese hamster ovary cell mutant (designated PGS-S) with a specific lesion in PGP synthase by using an in situ enzymatic assay for the enzyme. This mutant was obtained by introducing a second mutation into mutant PGS-P that had been generated by first-step mutagenesis. The PGP synthase activities in cell extracts of mutant PGS-S grown at 33 and 40 degrees C were 14 and 1% of those in the wild type cells, respectively; in addition, PGP synthase in cell extracts of mutant PGS-S exhibited higher sensitivity to heat than that of the wild type. Mutant PGS-S also showed a temperature-dependent defect in the synthesis of PG and CL in vivo, together with temperature sensitivity for cell growth. A temperature-resistant revertant of mutant PGS-S simultaneously restored PGP synthase activity and the ability to synthesize PG and CL in vivo to nearly the same levels as those of mutant PGS-P. These results constitute genetic evidence that PGP synthase is responsible for PG synthesis and is essential for cell growth.

Animals↗

Mitochondrial dysfunction of a cultured Chinese hamster ovary cell mutant deficient in cardiolipin.

In our preceding paper, we reported that a temperature-sensitive Chinese hamster ovary cell mutant, PGS-S, with thermolabile phosphatidylglycerophosphate synthase was defective in the biogenesis of both phosphatidylglycerol and cardiolipin (CL) at a nonpermissive temperature (Ohtsuka, T., Nishijima, M., and Akamatsu, Y. (1993) J. Biol. Chem. 268, 22908-22913). To investigate the biological role of cardiolipin, we examined the structure and function of mitochondria in mutant PGS-S cells, since CL is primarily found in the mitochondrial membranes of eukaryotic cells. Under conditions where the formation of CL was impaired, this mutant had both morphological and functional mitochondrial abnormalities, manifested by more stringent temperature sensitivity for cell growth in glucose-deficient medium and by reduced ATP production, increased glycolysis, and reduced oxygen consumption in intact cells. Rotenone-sensitive NADH oxidase activity in cell extracts was also reduced in the mutant cultivated at a nonpermissive temperature, showing a defect(s) in the respiratory electron transport chain of mitochondria. Of the respiratory chain complexes, rotenone-sensitive NADH-ubiquinone reductase (Complex I) was most severely impaired in the mutant, whereas its activity was restored in a revertant of the mutant that had regained the ability to synthesize CL. These results suggest that CL plays a critical role in mitochondrial functions, at least in the respiratory electron transport chain.

Adenosine Triphosphate↗

Sphingolipid deficiency induces hypersensitivity of CD14, a glycosyl phosphatidylinositol-anchored protein, to phosphatidylinositol-specific phospholipase C.

Strain SPB-1 is a temperature-sensitive Chinese hamster ovary cell mutant defective in sphingoid base biosynthesis. To examine the effects of sphingolipid deficiency on a glycosyl phosphatidylinositol-anchored protein, we constructed transfectants expressing mouse CD14 from the SPB-1 and the wild type cells. When the cells were precultured in a sphingolipid-deficient medium at 39 degrees C, CD14 expressed in the SPB-1 cells was hypersensitive to phosphatidylinositol-specific phospholipase C (PI-PLC), compared with that in the wild type cells. Moreover, after exposure of the cells to fumonisin B1, an inhibitor of ceramide synthase, CD14, even in the wild type cells, became hypersensitive to PI-PLC. The PI-PLC hypersensitivity in the SPB-1 cells was almost completely suppressed when the cells were cultured in the presence of exogenous sphingosine or sphingomyelin. On the other hand, the hypersensitivity induced by fumonisin B1 was suppressed by exogenous sphingomyelin but not by sphingosine. The suppression by exogenous glucosylceramide was partial under both conditions. Likewise, CD14 molecules in membranes prepared from the sphingolipid-deficient cells were more sensitive to PI-PLC than those from the control cells. These results indicated that a deficiency in cellular complex sphingolipids caused the PI-PLC hypersensitivity of CD14, suggesting the interaction of CD14 with sphingolipids in membranes.

Animals↗

A pathological study of intracranial posterior circulation dissecting aneurysms with subarachnoid hemorrhage: report of three autopsied cases and review of the literature.

Three autopsied cases of dissecting aneurysms with spontaneous subarachnoid hemorrhage of the intracranial posterior circulation are reported, and the literature is reviewed to investigate the pathological characteristics and pathogenesis of this lesion. The location and pathological features of the aneurysms were different in each of the cases presented. Subadventitial hemorrhage associated with the subarachnoid hemorrhage, multiple noncontiguous intramural hemorrhages, and new vessels in and around the arterial wall were noteworthy findings in our series. All 20 reported autopsied cases of the vertebrobasilar artery have a dissection between the media and adventitia with a rupture site in the thin adventitia. Seventeen of them had disruption of the entire arterial wall, but the remaining three cases had no apparent luminal connection. The clinicopathological features of this disease are various. On the basis of the pathological investigations of these reported cases, the pathogenesis of this lesion is discussed. Intramural hemorrhage associated with dissection without luminal connection should not be disregarded as a causative factor.

Aortic Dissection↗

Immunopharmacological characterization of a highly branched fungal (1-->3)-beta-D-glucan, OL-2, isolated from Omphalia lapidescens.

The immunopharmacological activities of a fungal (1-->3)-beta-D-glucan, OL-2, isolated from "Leiwan" Omphalia lapidescens were examined. Intraperitoneal (i.p.) administration of OL-2 to ICR mice induced a significant number of peritoneal exudate cells (PEC) and white blood cells over the period of a few days. Spleen cell numbers were also increased by i.p. administration of OL-2 at about a week. These changes reverted to the normal level within a month. Responses of spleen cells and bone marrow cells (BM) to colony stimulating factors (CSF) were augmented by OL-2 administration assessed by cell proliferation assay. Sera from OL-2 administered mice contained an increased concentration of colony stimulating activity. Gene expressions of interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha in the spleen were also increased. These results suggested the activation of hematopoietic responses, and would well relate to the incremental increase in PEC, white blood cell and spleen cell numbers. OL-2 also increased the serum concentration of fibronectin and complement component C-3. However, OL-2 did not show adjuvant activity to SRBC and antitumor activity against the solid form of Sarcoma 180 by i.p. administration. Yet, OL-2 did not interfere with the antitumor activity of SSG against the same tumor system. These facts suggested that OL-2 could enhance nonspecific host defense mechanisms by enhancing hematopoietic responses, but would not enhance or inhibit the specific immunity mediated by lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗