Biomedical subjects

M Nagashima

Publications and source records attributed to M Nagashima.

At least 73 records · Page 4Linked to original sources

PubMed1999

Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest. I. Gaseous microemboli.

OBJECTIVES: Recent studies suggest that myocardial reperfusion injury is exacerbated by free radicals when pure oxygen is used during cardiopulmonary bypass. Partial replacement of the oxygenator gas mixture with nitrogen, however, such as has already been adopted clinically in many centers, could increase the risk of gaseous nitrogen microembolus formation and therefore of brain damage because of the low solubility of nitrogen, particularly under conditions of hypothermia. METHODS: Ten 7- to 10-kg piglets were cooled for 30 minutes to 15 degrees C on cardiopulmonary bypass and then rewarmed for 40 minutes to 37 degrees C. In 5 piglets cardiopulmonary bypass was normoxic and in 5 it was hyperoxic. In each group 3 bubble oxygenators without arterial filters and 2 membrane oxygenators with filters were used. Cerebral microemboli were monitored continuously by carotid Doppler ultrasonography (8 MHz) and intermittently by fluorescence retinography. RESULTS: Embolus count was greater with lower rectal temperature (P <.001), use of a bubble oxygenator (P <.001), and lower oxygen concentration (P =.021) but was not affected by the temperature gradient between blood and body during cooling or rewarming. CONCLUSIONS: Gaseous microemboli are increased with normoxic perfusion, but this is only important if a bubble oxygenator without a filter is used.

Animals↗

PubMed1999

Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest. II. hypoxic versus free radical injury.

OBJECTIVES: Laboratory studies suggest that myocardial reperfusion injury is exacerbated by free radicals when pure oxygen is used during cardiopulmonary bypass. In phase I of this study we demonstrated that normoxic perfusion during cardiopulmonary bypass does not increase the risk of microembolic brain injury so long as a membrane oxygenator with an arterial filter is used. In phase II of this study we studied the hypothesis that normoxic perfusion increases the risk of hypoxic brain injury after deep hypothermia with circulatory arrest. METHODS: With membrane oxygenators with arterial filters, 10 piglets (8-10 kg) underwent 120 minutes of deep hypothermia and circulatory arrest at 15 degrees C, were rewarmed to 37 degrees C, and were weaned from bypass. In 5 piglets normoxia (PaO2 64-181 mm Hg) was used during cardiopulmonary bypass and in 5 hyperoxia (PaO2 400-900 mm Hg) was used. After 6 hours of reperfusion the brain was fixed for histologic evaluation. Near-infrared spectroscopy was used to monitor cerebral oxyhemoglobin and oxidized cytochrome a,a3 concentrations. RESULTS: Histologic examination revealed a significant increase in brain damage in the normoxia group (score 12.4 versus 8.6, P =.01), especially in the neocortex and hippocampal regions. Cytochrome a,a 3 and oxyhemoglobin concentrations tended to be lower during deep hypothermia and circulatory arrest in the normoxia group (P =.16). CONCLUSIONS: In the setting of prolonged deep hypothermia and circulatory arrest with membrane oxygenators, normoxic cardiopulmonary bypass significantly increases histologically graded brain damage with respect to hyperoxic cardiopulmonary bypass. Near-infrared spectroscopy suggests that the mechanism is hypoxic injury, which presumably overwhelms any injury caused by increased oxygen free radicals.

Animals↗

PubMed1999

A novel sialyl Lewis X analog attenuates cerebral injury after deep hypothermic circulatory arrest.

BACKGROUND: The initial step in the inflammatory process, which can be initiated by cardiopulmonary bypass and by ischemia/reperfusion, is mediated by interactions between selectins on endothelial cells and on neutrophils. We studied the effects of selectin blockade using a novel Sialyl Lewis X analog (CY-1503) on recovery after deep hypothermic circulatory arrest in a piglet model. METHODS: Twelve Yorkshire piglets were subjected to cardiopulmonary bypass, 30 minutes of cooling, 100 minutes of circulatory arrest at 15 degrees C, and 40 minutes of rewarming. Five animals received a bolus of 60 mg/kg of CY-1503 and an infusion (3 mg/kg per hour) for 24 hours from reperfusion (group O), and 7 randomly selected control piglets received saline solution (group C). Body weight and total body water content were evaluated 3 hours and 24 hours after reperfusion by a bio-impedance technique. Neurologic recovery of animals was evaluated daily by neurologic deficit score (0 = normal, 500 = brain death) and overall performance categories (1 = normal, 5 = brain death). The brain was fixed in situ on the fourth postoperative day and examined by histologic score (0 = normal, 5+ = necrosis) in a blinded fashion. RESULTS: Two of 7 animals in group C died. The neurologic deficit score was significantly lower in group O than in group C (postoperative day 1, P <.001; postoperative day 2, P =.02). The overall performance category was significantly lower in group O than in group C on postoperative day 2 (P =.01). Percentage total body water after cardiopulmonary bypass was significantly higher in group C than in group O (P =.03). Histologic score tended to be higher in group C than in group O, but this difference did not reach statistical significance (group O = 0.5 +/- 0.7; group C = 1.3 +/- 1.off CONCLUSION: Blockade of selectin adhesion molecules by saturation with a Sialyl Lewisx analog accelerates recovery after 100 minutes of deep hypothermic circulatory arrest in a piglet survival model.

Animals↗

PubMed1999

Down-regulated expression of glutamate transporter GLAST in Purkinje cell-associated astrocytes of reeler and weaver mutant cerebella.

The glutamate transporter plays an important role in rapid removal of glutamate from the synaptic cleft. Glutamate transporter GLAST is highly expressed in the Bergmann glia (BG), a unipolar cerebellar astrocyte associated structurally and functionally with Purkinje cells (PCs). Here we investigated the expression and localization in the reeler and weaver mutant cerebella with disorganized cytoarchitecture and disrupted synaptic circuitry. In the cortex of both cerebella, GLAST-expressing cells were astrocytes associating PCs; they were located around PC somata and primary dendrites, and extended glial fibrillary acidic protein (GFAP)-immunopositive processes surrounding PC somata and dendrites. Additional signals were detected in astrocytes of the reeler subcortex; they were dispersed among ectopic PCs and had GFAP-positive processes apposing to PC somata and stunted dendrites. Therefore, GLAST expression in PC-associated astrocytes was conserved in these mutants. Compared to the wild-type BG, however, the transcription level in individual mutant astrocytes was significantly reduced to about one-third level in the reeler and weaver cortex or one-sixth level in the reeler subcortex. Taking previous results on remarkable up-regulation during dendritogenic/synaptogenic stages and down-regulation following experimental glutamatergic denervation, it is suggested that GLAST expression in cerebellar astrocytes is regulated correlatively with cytological and/or synaptic differentiation of neighboring PCs.

ATP-Binding Cassette Transporters↗

PubMed1999

Inhibitory effects of anti-rheumatic drugs on vascular endothelial growth factor in cultured rheumatoid synovial cells.

Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and is constitutively expressed in the synovium of rheumatoid arthritis (RA). Over-expression of VEGF may play an important role in pathogenic vascularization and synovial hyperplasia of RA. In the present study, we examined whether disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX) and salazosulfapiridine (SASP), act by inhibiting the production of VEGF by cultured synovial cells of patients with RA. Treatment of cultured synoviocytes with lipopolysaccharide (LPS) significantly increased VEGF production by cultured synovial cells. BUC significantly inhibited LPS-induced VEGF production, while GST tended to inhibit the production of VEGF. The inhibitory effects on VEGF production were dose-dependent. In contrast, MTX and SASP did not affect VEGF production. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that BUC also inhibited LPS-induced VEGF mRNA expression in RA synovial cells. The present study provides the first evidence that BUC inhibits VEGF production and the expression of its mRNA in synovial cells of RA patients. Our results indicate that the anti-rheumatic effects of BUC are mediated by suppression of angiogenesis and synovial proliferation in the RA synovium through the inhibition of VEGF production by synovial cells.

Antirheumatic Agents↗

PubMed1999

The interaction of thrombomodulin with Ca2+.

Thrombomodulin (TM) is a cofactor for protein C activation by thrombin and each residue of a consensus Ca2+ site in the sixth epidermal growth factor domain (EGF6) is essential for this cofactor activity [Nagashima, M., Lundh, E., Leonard, J.C., Morser, J. & Parkinson, J.F. (1993) J. Biol. Chem. 268, 2888-2892]. Three soluble analogs of the extracellular domain of TM, solulin (Glu4-Pro490), TME1-6 (Cys227-Cys462) and TMEi4-6 (Val345-Cys462) were prepared for equilibrium dialysis experiments by exhaustive dialysis against Ca2+-depleted buffer. However, all three analogs still contained one tightly bound Ca2+ (Kd approximately 2 microm), which could only be removed by EDTA. Epitope mapping with Ca2+-dependent monoclonal antibodies to EGF6 provided further localization of this tight Ca2+ site. Equilibrium dialysis of the soluble TM analogs in [45Ca2+] between 10 and 200 microm revealed a second Ca2+ site (Kd = 30 +/- 10 microm) in both solulin and TME1-6, but not in TMEi4-6. Ca2+ binding to this second site was unaffected by bound thrombin and we attribute it to the consensus Ca2+ site in EGF3. A 75-fold decrease in the binding affinity of thrombin to TM was observed with immobilized solulin treated with EDTA to remove the high affinity Ca2+ by measuring kassoc and kdiss rates in a BIAcoretrade mark instrument. Ca2+-dependent conformational transitions detected by CD spectroscopy in the far UV indicate a more ordered structure upon Ca2+ binding. Bound Ca2+ stabilized soluble TM against protease digestion at a trypsin-like protease-sensitive site between Arg456 and His457 in EGF6 compared with protease treatment in EDTA. Finally, TM containing EGF domains 4-6, but lacking the interdomain loop between EGF3 and 4 (TME4-6), has an identical Ca2+ dependence for the activation of protein C as found for TMEi4-6, indicating this interdomain loop is not involved in Ca2+ binding.

Animals↗

PubMed1999

Effects of exercise for 1 month on serum lipids in adolescent females.

BACKGROUND: The present study was done to clarify the effects of 1 month of exercise on levels of total cholesterol (TC) and high-density lipoprotein cholesterol (HDLC) and on the ratio TC/HDLC and also to evaluate the relationship of body fat to amount of exercise and TC/HDLC ratio. METHODS: Twenty-seven female athletes (aged 15-18 years) were divided into two groups: the participant's group, in which players trained and attended a tournament, and the non-participant's group, in which players did not attend the tournament. We assessed the amount of exercise, body composition, serum TC and HDLC and TC/HDLC on four occasions: before (T0), during (T1), 1 day after (T2) and a week after (T3) the experimental period. Levels of TC and HDLC adjusted for changes in plasma volume were compared for each occasion. Two multiple regression models for change in TC/HDLC from T0 to T2 and from T0 to T3 were employed. RESULTS: (i) The changing patterns in TC and HDLC throughout the program were different between the two groups; (ii) the decreased level of TC/HDLC after 1 month of exercise may easily revert to its original level; and (iii) the relevant factor for the decline in TC/HDLC was the amount of exercise, not body fat reduction. CONCLUSIONS: Exercise may be a more important factor for the improvement of TC/HDLC than concomitant body fat reduction and non-strenuous exercise may maintain a more stable and higher HDLC level than strenuous exercise.

Adolescent↗

PubMed1999

Significance of the atherosclerogenic index and body fat in children as markers for future, potential coronary heart disease.

BACKGROUND: The purpose of this study is to establish a simple marker in children for future, potential risks of coronary heart disease. METHODS: We measured serum total cholesterol (TC) and triglyceride (TG) by enzymatic methods, high-density lipoprotein cholesterol (HDLC) by the dextran sulfate-magnesium method and estimated body fat by the new impedance method in 1289 children (651 boys and 638 girls) in the fourth grade (9 or 10 years old) to obtain the atherosclerogenic index (AI). We also investigated the children's lifestyle. RESULTS: The probability of an AI score of 3 or more was significantly higher in children with an estimated 23-25% body fat than in those with body fat less than 17%. Moreover, the odds ratio increased along with an increase in the percentage of body fat. When body fat was estimated as being greater than 29%, the odds ratio was 11-fold higher than those with body fat less than 17%. When body fat was greater than 23%, the children's physical activity, as assessed by the questionnaire, was found to be poorer than those with lower body fat. Levels of TC and TG were significantly higher and that of HDLC was lower in those with less body fat. CONCLUSIONS: The AI is a useful indicator of obesity in children. The combination of AI and percentage body fat is a good indicator for evaluating children who would be at a greater risk of obesity, hyperlipidemia, unhealthy eating habits and inadequate physical activity. The hypothetical risk levels for future coronary heart disease are an AI score of > or = 3 and percentage body fat > or = 23% in Japanese children.

Arteriosclerosis↗

PubMed1999

Isolation of a Kawasaki disease-associated bacterial sequence from peripheral blood leukocytes.

BACKGROUND: The clinical and epidemiologic features of Kawasaki disease (KD) suggest an infectious etiology, but the agent(s) remains unknown. We aimed to isolate the causative bacterial gene from peripheral blood leukocytes of patients with acute KD. METHODS: Nested polymerase chain reaction (PCR) assay was used to amplify the bacterial 16S ribosomal RNA gene (rDNA). The amplified DNA were cloned into a plasmid vector and sequenced. Phylogenetic analysis was performed with clustal W program and the neighbour-joining method. RESULTS: First, the PCR reagents were examined by the PCR assay using conservative primers and we found more than 10 16S rDNA sequences contaminating the reagents. We then examined five KD patients using the PCR assay, excluding the contaminated sequences, and obtained five 16S rDNA sequences as possible KD-associated sequences. The primers specific to each 16S rDNA sequence were synthesized and used for specific PCR assays. Only the PCR assay specific to the 16S rDNA sequence termed 16S71-33 did not show any false positives with the control DNA from non-KD patients. The 16S71-33 sequence was positive in three of 20 patients with acute KD before gamma-globulin therapy, but it became negative after therapy. The phylogenetic analysis showed a new species of the genus Corynebacterium as the origin of the 16S71-33 sequence. CONCLUSIONS: These data show that an infectious KD agent is traced in peripheral leukocytes and that a new Corynebacterium species may be responsible for KD in some cases. The true frequency and the role of the new Corynebacterium in KD would be clarified by measuring specific antibodies to it.

Base Sequence↗

PubMed1999

Sudden death in school children: role of physical activities and meteorological conditions.

BACKGROUND: This current study is aimed at investigating the effect of physical activities and meteorological conditions on the sudden deaths of children without obvious causes at school. METHODS: The subjects are 76 victims of sudden death at school in the 12 years from 1983 to 1994 in Aichi Prefecture, Japan. The incidence of these sudden deaths is shown by month of the year, day of the week and hour of the day in relation to physical activities and meteorological factors. The analysis of Hayashi's quantitation type II was used for evaluation of the relationship between sudden deaths under the different physical conditions, such as sedentary (at rest or slow walking) or active (running, competitive sports or swimming) conditions, and meteorological or weather factors such as, season of the year, wind-chill factor, atmospheric pressure and relative humidity. RESULTS: Of 76 cases, 21 died suddenly under sedentary physical conditions and 55 under active conditions. The incidence of sudden death was highest from 10.00 to 11.00 h and on Thursday. Sudden death under sedentary conditions was associated with autumn and winter or with winter with high humidity and low atmospheric pressure. Sudden deaths during running were associated with spring with low humidity and high pressure and sudden deaths during competitive sports were associated with dry and cloudy weather. CONCLUSION: Sudden deaths in children at school may be associated with physical activities and meteorological conditions.

Cause of Death↗

PubMed1999

Role of the oxygen uptake efficiency slope in evaluating exercise tolerance.

OBJECTIVE: To investigate the interprotocol agreement of oxygen uptake efficiency slope (OUES). METHODS: 16 Japanese children and adolescents (10 boys and six girls) underwent two sessions of maximal exercise testing according to the following two treadmill protocols: the standard Bruce protocol and the rapidly increasing staged (RIS) protocol. Maximal oxygen uptake (VO2max), the ventilatory anaerobic threshold (VAT), and the OUES were obtained from the gas analysis data. Agreement between the protocols was tested by means of the Bland-Altman method. RESULTS: Interprotocol agreement was excellent for the OUES (limit of agreement, -18% to 17% of the mean value), slightly less good for VO2max (limit of agreement, -20% to 24% of the mean value), and poor for the VAT (limit of agreement, -31% to 31% of the mean value). CONCLUSION: These results confirm the clinical usefulness of the OUES as a measure of evaluating exercise tolerance in the paediatric population.

Adolescent↗

PubMed1999

Anatomical variations in the origin of the human ophthalmic artery with special reference to the cavernous sinus and surrounding meninges.

The origin of the human ophthalmic artery (OA) and surrounding structures was investigated in 109 cadavers by three different methods: macroscopic, stereomicroscopic, and histological observations. The following results were obtained. (1) Macroscopic observation: In 39% of the specimens the origin of the OA was observable in the cranial cavity and defined as the intradural (i.d.) type. The other 61% were named the extradural (e.d.) type. (2) Stereomicroscopic observation: In 59% of the cases, the OA originated from the internal carotid artery over or on the cavernous roof and at least a part of the OA was exposed within the cranial cavity. In the other 41% the OA originated within the cavernous wall or cavity and entered directly the optic dural sheath, thus no part of the OA was visible in the cranial cavity. Therefore, approximately 20% of the origins of the OA might be of the i.d. type, although they could not be macroscopically identified in the cranial cavity since they might emanate from the internal carotid artery between the optic canal and the optic nerve, even above the cavernous roof. (3) Histological observation: The proximal portion of the OA runs alongside the optic nerve within the subarachnoid space in the cases of the i.d. type. In contrast, the corresponding portion of the e.d. type was embedded in the dense fibrous tissue which was continuous both with the dura mater of the cavernous wall and the periosteum of the sphenoid. These anatomical data may provide important information for understanding the variety of the pathology in this region and is also useful for designing operative strategies.

Adolescent↗

PubMed1999

Surgical anatomy for direct hypoglossal-facial nerve side-to-end "anastomosis".

OBJECT: In this study the authors investigated the histomorphometric background and microsurgical anatomy associated with surgically created direct hypoglossal-facial nerve side-to-end communication or nerve "anastomosis." METHODS: Histomorphometric analyses of the facial and hypoglossal nerves were performed using 24 cadaveric specimens and three surgically obtained specimens of severed facial nerve. Both the hypoglossal nerve at the level of the atlas and the facial nerve just distal to the external genu were monofascicular. The number of myelinated axons in the facial nerve (7228 +/- 950) was 73.2% of those in the normal hypoglossal nerve (9778 +/- 1516). Myelinated fibers in injured facial nerves were remarkably decreased in number. The cross-sectioned area of the normal facial nerve (0.948 mm2) accounted for 61.5% of the area of the hypoglossal nerve (1.541 mm2), whereas that of the injured facial nerve (0.66 mm2) was less than 50% of the area of the hypoglossal nerve. Surgical dissection and morphometric measurements were performed using 18 sides of 11 adult cadaver heads. The length of the facial nerve from the pes anserinus to the external genu ranged from 22 to 42 mm (mean 30.5 +/- 4.4 mm). The distance from the pes anserinus to the nearest point on the hypoglossal nerve ranged from 14 to 22 mm (mean 17.3 +/- 2.5 mm). The former was always longer than the latter; the excess ranged from 6 to 20 mm (mean 13.1 +/- 3.4 mm). Surgical anatomy and procedures used to accomplish the nerve connection are described. CONCLUSIONS: The size of a half-cut end of the hypoglossal nerve matches a cut end of the injured facial nerve very well. By using the technique described, a length of facial nerve sufficient to achieve a tensionless communication can consistently be obtained.

Accessory Nerve↗

PubMed1999

[Cardiac events in vasospastic angina: site and morphology of coronary artery spasm is related to the long-term prognosis of vasospastic angina].

To determine whether the site and morphology of coronary artery spasm provoked with acetylcholine can predict the long-term prognosis of vasospastic angina, coronary artery spasm (more than 90% narrowing) provoked with acetylcholine was studied in 66 consecutive patients (56 males, 10 females, mean age 56 +/- 9 years) with vasospastic angina. All patients were followed for 6.7 +/- 0.9 years and the incidence of cardiac events such as sudden death, myocardial infarction or worsened unstable angina was compared with the site and morphology of provoked spasm. The site of spasm was regarded as proximal when spasm occurred in the proximal site of 3 major coronary arteries which was designated as segment 1, 6 or 11, according to the classification of the American Heart Association, and distal in other segments. The morphology of spasm was classified into 3 types, focal (12 cases, localized more than 90% narrowing with adjoining parts constricting less than 25%), diffuse (17 cases, diffuse more than 90% narrowing), and intermediate (37 cases, localized more than 90% narrowing with adjoining parts constricting 25-90%). The site of spasm was classified into 2 types, the proximal group (24 cases) and the distal group (42 cases). Cardiac events occurred in 7 patients during the follow-up period: sudden death in 2, myocardial infarction in 2, and worsened unstable angina in 3. As to the site of spasm, the incidence of cardiac events was 21% (5/24 patients) in the proximal group, significantly higher than 5% (2/42) in the distal group (p < 0.05). As to the site of spasm, the incidence of cardiac events was 41% (5/12) in the focal group, significantly higher than 3% (1/37) in the intermediate group and 6% (1/17) in the diffuse group (p < 0.001). The presence of proximal and focal coronary artery spasm was associated with a significantly higher incidence of cardiac events. The site and morphology of coronary artery spasm provoked with acetylcholine is related to the long-term prognosis of vasospastic angina.

Acetylcholine↗

PubMed1999

Longterm outcome of total joint arthroplasty in nonambulatory patients with rheumatoid arthritis.

OBJECTIVE: To assess the outcome of minimum 10 year followup of total joint arthroplasty (TJA) in nonambulatory patients with rheumatoid arthritis (RA). METHODS: TJA was performed in 40 nonambulatory patients with RA who satisfied the following criteria: (1) strong motivation; (2) good relationship with our medical staff; (3) no marked cervical cord lesion: (4) absence of severe systemic complications. These included 38 women and 2 men whose average age at the initiation of TJA was 58.8 years. The duration of time between loss of walking ability and surgery was 2 months to 5 years. Average hospitalization time was 4.5 months. Followup after the last surgery was 10 to 18 years. RESULTS: One year after the last surgery, 28 of the 40 patients could walk outdoors again, 11 indoors, and one was still unable to walk. By 5 years after surgery, 9 patients had died of diseases unrelated to surgery. Of the remaining 31 patients, 19 could walk outdoors, 10 indoors, and 2 could not walk. Deterioration of walking was observed in 13 patients (41.9%) compared with one year after surgery. By 10 years after surgery, 32 patients had died of diseases unrelated to surgery, 4 could walk outdoors, 4 indoors. Of these, 4 patients (50%) had worsened in walking ability compared with one or 5 years after surgery. Major complications of TJA were observed in 12 patients. These were femoral neck fractures in 3, supracondylar femoral fractures in 3, loosening of the acetabulum socket in 4, loosening of the femoral hip prosthesis in 2. CONCLUSION: TJA should be a useful treatment for restoration of walking in nonambulatory patients with RA. However, even after TJA, walking ability deteriorated in about half of the patients as the duration of followup observations exceeded 5 years.

Adult↗

PubMed1999

The human and rat recombinant receptors for advanced glycation end products have a high degree of homology but different pharmacokinetic properties in rats.

The accelerated formation of advanced glycation end products (AGEs) is implicated in diabetic microvascular and macrovascular complications. The binding of AGEs to their cellular surface receptor (RAGE) induces vascular dysfunction and in particular an increase in vascular permeability. We previously demonstrated that rat recombinant RAGE (rR-RAGE) produced in insect cells corrected the hyperpermeability due to RAGE-AGE interaction and that pharmacokinetic properties of rR-RAGE after i.v. administration in rats were compatible with a potential therapeutic use. In the present study, we showed that recombinant human RAGE (rH-RAGE) had a similar efficacy in inhibiting AGE-induced endothelial alteration and in reducing the hyperpermeability observed in streptozotocin-induced diabetic rats. (125)I-rH-RAGE elimination half-life after i.v. administration was similar in diabetic and normal rats (53.7 +/- 7.6 and 45.3 +/- 4.0 h, respectively). The presence of AGEs is responsible for a higher distribution volume in diabetic rats compared with normal rats (15.3 +/- 2.7 and 7.7 +/- 0. 7 l/kg, respectively). Immunoreactive (125)I-rH-RAGE decreased more rapidly than did immunoreactive (125)I-rR-RAGE. The differences between (125)I-rH-RAGE and (125)I-rR-RAGE pharmacokinetics in rat may be related to differences in potential O-glycosylation and protease cleavage sites between the two RAGE molecules.

Albumins↗

PubMed1998

Role of basic fibroblast growth factor in the pathogenesis of moyamoya disease.

The pathogenesis of moyamoya disease is still under investigation. In this study, the authors focus on the role of cytokines in the pathogenesis of moyamoya disease by using immunohistochemical analyses. The authors examined two specimens in the circle of Willis obtained at autopsy from two patients with moyamoya disease and two additional specimens obtained from control cadavers with atherosclerotic stenosis of the intracranial carotid arteries. Immunohistochemical examinations of the sections of the major intracranial arteries were performed using antismooth muscle cells (SMCs), monocytes, growth factor, cell nuclear antigen, and fragmented DNA antibodies. Basic fibroblast growth factor (bFGF) staining was present only in the endothelial cells of the moyamoya disease specimens and was not seen in control samples. In addition, the endothelial cells and SMCs in the media were positive for terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick-end labeling of fragmented DNA method but not in the SMCs in the intima in moyamoya disease specimens, which indicates that an apoptotic process is active in only SMCs in the media but not in the intima. In conclusion, it is suggseted that the presence of bFGF in the media specifically seen in moyamoya disease suppresses the apoptotic process of SMCs in the intima.

Journal Article↗

PubMed1998

High-volume continuous hemofiltration during cardiopulmonary bypass attenuates pulmonary dysfunction in neonatal lambs after deep hypothermic circulatory arrest.

BACKGROUND: Cardiopulmonary bypass (CPB) induces an inflammatory reaction that activates neutrophils and releases free radicals in tissue. Ischemia-reperfusion further aggravates inflammation. Hemofiltration (HF) could potentially remove inflammatory mediators and reduce injury. This study assessed the effect of continuous high-volume HF during CPB on systemic edema formation and pulmonary function after deep hypothermic circulatory arrest (DHCA). METHODS AND RESULTS: Anesthetized lambs (n = 16) underwent CPB with systemic cooling (40 minutes), DHCA (120 minutes at 18 degrees C), and rewarming (40 minutes). All animals were weaned from CPB and observed for 3 hours after reperfusion. Continuous HF was used in 8 lambs at a flow rate of 300 mL/kg per hour throughout CPB, simultaneously replacing hemofiltration volume with a balanced salt solution (HF group). In 8 control animals, no hemofiltration was performed. Hematocrit remained at 23% to 25% during the experiment in both groups. Pulmonary vascular resistance (PVR), lung dynamic compliance (Cdyn), alveolar-arterial oxygen difference (AaDO2), and total body water content (bioimpedance) were measured. Malondialdehyde (MDA), a product of lipid peroxidation, was assayed in lung tissue. Percent increase of body water content at 180 minutes of reperfusion was significantly lower in the HF group than in control (132 +/- 2% vs 152 +/- 5%, P < 0.005). There was less of a rise in PVR compared with baseline at 180 minutes of reperfusion in the HF group than in control (131 +/- 8% vs 238 +/- 26%, P < 0.005). In addition, percent recovery of Cdyn and AaDO2 in the HF group was preserved significantly (respectively, P < 0.05) 2 hours after reperfusion than in the control group. Lung tissue MDA in the HF group (46.2 +/- 12.6 vs 65.3 +/- 17.1 nmol/L per gram of tissue, P < 0.05) was significantly lower than in the control group. CONCLUSIONS: High-volume, continuous hemofiltration during CPB attenuates systemic edema formation, pulmonary hypertension, the extent of lung dysfunction, and depression of cardiac output and reduces free radical-mediated tissue injury after CPB with DHCA. This technique may have a clinical application to reduce the morbidity rate of CPB.

Animals↗