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Biomedical subjects

H Sakai

Publications and source records attributed to H Sakai.

At least 235 records · Page 13Linked to original sources
PubMed2000

Platelet surface P-selectin molecules increased after exposing platelet to a high shear flow.

BACKGROUND: P-selectin is known to play a crucial role in leucocyte recruitment at sites of vascular injury. Although platelet surface expression of P-selectin molecules are well known to occur after platelet stimulation by chemical agonists such as alpha-thrombin, it is still uncertain whether P-selectin expression occurs in the process of the more physiological platelet activation pathway mediated by interaction between von Willebrand factor (vWF) and platelet receptor proteins, including glycoprotein (GP) Ibalpha and GP IIb/IIIa, occurring under high shear rates generated by blood flow. METHODS: We have developed a method to detect P-selectin molecules expressed on platelet surface with flow-cytometer and monoclonal antibody, which can bind exclusively to P-selectin (WGA1), directly conjugated with fluorescein isothiocynate. This method allowed us to measure platelet surface P-selectin molecules semiquantitatively. RESULTS: We demonstrated that a significant increase in platelet surface P-selectin molecules occur after exposing platelets to a relatively high shear rate of 10,800 s(-1). We have also demonstrated that shear-induced surface expression of P-selectin as well as microparticle release from platelets depended at least on the interaction between von Willebrand factor and glycoprotein Ibalpha, a platelet surface receptor for the former. CONCLUSIONS: Shear-induced von Willebrand-mediated surface expression of P-selectin may play a role in leucocyte recruitment in platelet thrombi at vascular injury sites.

Antibodies, Monoclonal↗
PubMed2000

Plasma concentration of von Willebrand factor in acute myocardial infarction.

Recent investigations have revealed the crucial role of von Willebrand factor (vWF) in platelet thrombus formation under flow conditions. The plasma concentrations of vWF were measured together with various hemodynamic and hemostatic parameters in 51 cases of acute myocardial infarction. In 10 randomly selected cases, the plasma concentrations and distribution of multimers vWF were serially determined after reperfusion therapy by percutaneous transluminal coronary angioplasty (PTCA). The vWF concentration at the onset of the acute myocardial infarction was significantly higher than in an age-matched control group (vWF AG: 18.7 +/- 1.2 microg/ml vs. 10.3 +/- 0.5 microg/ml, p = 8.43 x 10-(12), mean +/- SE). Simultaneous determination of hemodynamic and hemostatic parameters revealed that the only two parameters that were significantly correlated with the patients' plasma vWF concentrations were their pulmonary capillary wedge pressure (PCWP) and heart rate, suggesting a relationship between hemodynamic changes induced by the onset of myocardial infarction and the vWF plasma concentrations. Serial determinations revealed that the vWF concentrations had not changed 1 h after reperfusion therapy, but that they significantly increased by 24 to 72 h. The distribution of the larger multimers of vWF also increased in the acute and subacute phase. The vWF concentration and multimer distribution normalized 14 days after the onset of the myocardial infarction. Our findings suggest that the vWF concentration increased in acute myocardial infarction patients, possibly in association with the hemodynamic deterioration that occurs in acute myocardial infarction.

Adult↗
PubMed2000

Inhibition of thromboxane A(2)-induced Cl(-) secretion by antidiarrhea drug loperamide in isolated rat colon.

The antitumor drug irinotecan clinically causes severe diarrhea as a side effect. Thromboxane A(2) (TXA(2)), released by irinotecan, has been shown to be a novel physiological stimulant of Cl(-) secretion in the rat colon. Herein, we examined the effect of loperamide, an antidiarrhea drug, on Cl(-) secretion induced by irinotecan; 9, 11-epithio-11,12-methano-thromboxane A(2) (STA(2)), a stable TXA(2) analog; and prostaglandin E(2) (PGE(2)) by using isolated mucosae of the rat colon. In the presence of atropine, loperamide in a concentration-dependent manner inhibited the Cl(-) secretion induced by irinotecan, STA(2), and PGE(2). However, the drug inhibited more effectively the irinotecan- and STA(2)-induced secretion (IC(50) = 0. 7 and 1.2 microM, respectively) than the PGE(2)-induced secretion (IC(50) = 23 microM). Naloxone, an opiate antagonist, did not affect the antisecretory action of loperamide. Similar to the case for loperamide, W-7, a specific calmodulin antagonist, inhibited more effectively the STA(2)-induced Cl(-) secretion (IC(50) = 5 microM) than the PGE(2)-induced secretion (IC(50) = 36 microM). W-5, a low-affinity calmodulin antagonist (a dechlorinated control analog of W-7), also inhibited the STA(2)-induced secretion, but this effect was much less than that of W-7. STA(2)-induced increase in the intracellular free Ca(2+) concentration of single colonic crypt cells was not affected by loperamide. We suggest that loperamide efficiently inhibits the TXA(2)-induced secretion by blocking the calmodulin system in the colonic epithelium. The present results may explain why coadministration of loperamide with irinotecan is clinically efficient for avoiding the irinotecan-induced side effect of diarrhea.

Animals↗
PubMed2000

[Brain death in pediatric patients--from the viewpoint of pediatric intensive care].

In Japan, "brain death" has been discussed exclusively in connection with organ transplantation. However, the concept of brain death, which emerged with the progress in intensive care medicine, should be discussed in the context of palliative care in the ICU. It should be recognized that intensive care medicine includes not only life-saving high-tech therapeutic modalities, but also ethical and psycho-social aspects of modern medicine. In order to find out a decent solution to pediatric brain death issues, it is essential to develop pediatric intensive care in Japan.

Brain Death↗
PubMed2000

PSP94 expression after androgen deprivation therapy: a comparative study with prostate specific antigen in benign prostate and prostate cancer.

PURPOSE: To examine the clinical use of PSP94 (prostate secretory protein of 94 amino acids) as an androgen independent marker, we conducted a comparative study of prostate samples including benign tissue and cancers which did and did not have androgen deprivation. MATERIALS AND METHODS: Among 163 radical prostatectomy cases 75 had androgen deprivation before operation, while surgery was performed in the remainder without prior hormone treatment. Considering the pathological up grading following hormone therapy, contiguous sections from radical prostatectomy samples were stained for PSP94 and prostate specific antigen (PSA) by immunohistochemistry, and equivalent tumor foci were evaluated by assessing the intensity and extent of the staining. RESULTS: In untreated benign prostate tissue PSP94 and PSA staining was positive and identical in all sections in the no pretreatment group. However, PSP94 expression in the androgen deprivation group was significantly higher than PSA in intensity (p = 0.0005) and extent (p = 0.034). In untreated cancer cases PSP94 intensity and extent demonstrated strong inverse association with Gleason grade (p <0.0001). In contrast, PSA expression was high in every grade, resulting in no statistical association with tumor grade. In the androgen deprivation group PSA staining was decreased in every grade compared to the no pretreatment group. On the other hand, PSP94 expression was decreased in grade 3 tumor foci but increased in grades 4 and 5 tumor foci compared with samples of the corresponding grade in the no pretreatment group (p = 0.0034). CONCLUSIONS: PSP94 expression in benign prostate persists under androgen deprivation compared to PSA. PSP94 synthesis in high grade tumor appears to be activated in the absence of androgen stimulation, indicating the possible alternative pathways in the regulation of PSP94.

Adenocarcinoma↗
PubMed2000

[Combined endovascular stent implantation and coil embolization for the treatment of a vertebro-basilar fusiform aneurysm: technical case report].

We describe a case of the combined application of endovascular stent implantation and Guglielmi detachable coil packing for the treatment of a vertebro-basilar fusiform aneurysm and review the literature on stent placement to treat cerebral aneurysms. A 70-year-old female presented with an acute headache from subarachnoid hemorrhage. A fusiform aneurysm with a broad-based neck and dome, measuring 15 mm, involving the union of the vertebral arteries and the proximal basilar artery was demonstrated on cerebral angiography. The aneurysm was judged to be inoperable and treated conservatively. Twelve days later the patient was transferred to our hospital for endovascular therapy. An intravascular stent (MultiLink) was placed across the base of the aneurysm through the right vertebral artery. After this, coil placement in the aneurysm around the stent was performed via a microcatheter guided from the left vertebral artery. After that a microcatheter was guided from the right vertebral artery through the interstices of the stent into the aneurysm, and additional coils were placed. Final angiography showed subtotal occlusion of the aneurysm and excellent blood flow of the parent artery through the stent. There were no new neurological deficits. Neither rerupture nor ischemic event has occurred. The use of stents provides another treatment for managing the difficult entity of intracranial aneurysms.

Acute Disease↗
PubMed2000

[Porencephaly].

Explore the source record for details and available documents.

Brain↗
PubMed2000

Ampullectomy of carcinoma of the papilla of vater in an elderly patient without jaundice.

A 79 year-old woman was admitted to Aioi City Hospital for a closer examination of hepatic dysfunction. A filling defect was observed at the distal end of the intrapancreatic common bile duct by computed tomography combined with drip infusion cholangiography. The diagnosis of adenoma with dysplasia at the papilla of Vater was obtained by a biopsy performed during duodenoscopy. As a result, we performed an ampullectomy. Histologic examination revealed a papillary adenocarcinoma which partly extended just beyond the muscle of Oddi. The patient made an uneventful recovery and was discharged on the 35th postoperative day. Here, based upon our experience, we discuss such problems as the accuracy of preoperative diagnosis and the indications for ampullectomy.

Adenocarcinoma, Papillary↗
PubMed2000

Efficacy of a new hemostatic device, Adapty , after transradial coronary angiography and intervention.

A novel hemostatic device, Adapty (Medikit, Tokyo, Japan), was developed to achieve effective and comfortable hemostasis following transradial procedures. The device consists of a pad fixed to a transparent plastic plate and a self-adhesive strap. The catheter sheath is removed from the radial artery after the pad has been positioned precisely over the puncture site, with the strap attached to the plate. Compression pressure then is adjusted with the self-adhesive strap, as is required with occlusive clamps. Patients do not need to maintain hyperextension of the wrist after the procedure. The wrist can be mobilized immediately after application. The efficacy of Adapty was evaluated in prospective observations of 200 patients. The device was successfully applied in all patients immediately after sheath removal. No patient required interruption of compression because of pain, congestion or ischemia. Complete hemostasis was obtained in 199 patients (99.5%), and the device caused no vascular complications. This study demonstrates that Adapty is highly effective for achieving hemostasis after transradial procedures.

Aged↗
PubMed2000

[A new method for pharmacokinetic analysis of 99mTc-GSA using two-compartment and two-parameter model].

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a liver scintigraphy agent which binds to asialoglycoprotein receptor in hepatocyte. Twenty-six patients with liver dysfunction were examined with 99mTc-GSA liver scintigraphy using two-compartment and two-parameter model (2C2P model). The 99mTc-GSA was assumed to move within two compartments (whole blood and liver). k1 and k2 were parameters which represented transfer rate constant from blood to liver, and from liver to blood, respectively. Two differential equations based on 2C2P model were integrated, so that k1, k2, k1/k2 and VLmg were estimated from the time-activity curves of the heart and liver. VLmg was computed as maximum amount of 99mTc-GSA binding to liver. The results were compared with the liver function tests and the conventional 99mTc-GSA indices: HH15, LHL15, and LU15. k1/k2 and VLmg values had positive correlation with the result of the serum liver function tests, Plt., T.Bil., ChE, GOT, LDH, ALP and gamma GTP. It is concluded that this new method using 2C2P model is not invasive and simplest in the 99mTc-GSA liver scintigraphies, and may be useful in evaluating liver function.

Adult↗
PubMed2000

[A case with juvenile rheumatoid arthritis who developed cerebral vasculitis and venovascular hypertension].

On November, 1997, a 15-year-old boy visited our hospital because of headache, fever and arthralgia. He was treated with 5 mg/day of prednisolone thereafter. On October 21, 1998, he was admitted because of remittent fever and multiple arthralgia and diagnosis of juvenile rheumatoid arthritis (JRA) was made. He was also found to have hypertension of 210/110 mmHg, and soon developed ptosis of the eye, facial paresis and perceptive deafness of the right side. Cerebrospinal fluid showed protein of 98 mg/dl and mildly elevated IgG, IgA and IgM levels with normal cell count. Brain MRI examination revealed multiple cerebral lesions in the frontal, parietal and cerebellar areas on the right, whose cause was thought to be vasculitis. Renal angiography demonstrated a right renal artery stenosis, compatible with renovascular hypertension. He was treated with 60 mg of prednisolone per day, which brought about a satisfactory improvement of the above rheumatic and neurologic signs. On November 17, 1998, he received a follow-up study of MRI, which failed to show any cerebral lesions, supporting the effectiveness of prednisolone. An angiotensin converting enzyme inhibitor successfully normalized hypertension and renin activity in serum, although renal blood flow did not increase.

Adolescent↗
PubMed1999

Inhibition of caspase cascade by HTLV-I tax through induction of NF-kappaB nuclear translocation.

NF-kappaB is required for prevention of apoptosis. We examined the importance of human T-cell leukemia virus-I (HTLV-I) Tax protein to stimulate NF-kappaB nuclear translocation, thus preventing apoptosis. Jurkat cells and JPX-9 cells in which the inducible Tax expression plasmid vector was stably transfected were used in the present study. Both Jurkat and Tax(-) JPX-9 cells had small amounts of basal nuclear NF-kappaB activity. The addition of NF-kappaB inhibitors suppressed NF-kappaB nuclear translocation of the cells, thus inducing apoptosis. Sequential activation of caspases from caspase-8 to caspase-3 was shown during this process. NF-kappaB nuclear translocation in JPX-9 cells was stimulated through Tax expression, and both the activation of caspases and apoptosis induced by NF-kappaB inhibitors were significantly suppressed in the Tax(+) JPX-9 cells. The expression of Bcl-2, Bax, and Bcl-x was not changed among Jurkat, Tax(-) JPX-9, and Tax(+) JPX-9 cells in the presence or absence of NF-kappaB inhibitors. X-chromosome-linked inhibitor of apoptosis (XIAP) protein expression in Tax(-) JPX-9 cells was significantly suppressed by NF-kappaB inhibitors, however, its expression in Tax(+) JPX-9 cells was maintained even by the addition of NF-kappaB inhibitors. Our results suggest that the activation of NF-kappaB via Tax protein in HTLV-I infected cells renders the cells resistant to apoptosis. The expression of anti-apoptotic gene products such as XIAP to suppress caspase cascade, results in an increase of cytokine production and cell proliferation; one of the proposed mechanisms that promotes autoimmune disorders such as Sjögren's syndrome and rheumatoid arthritis found in HTLV-I seropositive subjects.

Apoptosis↗
PubMed1999

TRH increases cerebrospinal fluid concentration of kynurenine.

We have analyzed changes in cerebrospinal fluid (CSF) concentrations of monoamine-related substances to clarify the mechanism of the antiepileptic action of thyrotropin-releasing hormone (TRH). TRH-tartrate was administered to 14 patients with intractable epilepsy. Before and 2 weeks after TRH administration, CSF was collected and analyzed for tryptophan and tyrosine metabolites. Among monoamine-related substances, only CSF concentrations of kynurenine were increased after TRH therapy. Considering the fact that kynurenic acid acts as antagonist on the NMDA receptor complex, the results of this study may explain at least one of the mechanisms of the effectiveness of TRH therapy for intractable epilepsy.

Adolescent↗
PubMed1999

Identification of two distinct transcripts for the neuronal apoptosis inhibitory protein gene.

The spinal muscular atrophies (SMA), characterized by motor neuron loss and progressive paralysis, are among the most common autosomal recessive disorders. Recently, two SMA candidate genes, NAIP (neuronal apoptosis inhibitory protein) and survival motor neuron (SMN), were reported and a 131-kb genomic sequence of 5q13.1 encompassing these two genes was determined. Based upon this genomic sequence, the original NAIP cDNA sequence published in 1995 was shown to contain foreign fragments. We therefore conducted an extensive cDNA cloning of NAIP from a human fetal brain library. Our studies confirmed that the cDNA sequence deduced from the 131-kb genomic sequence was the major transcript in the human fetal brain. In addition, a shorter and minor transcript was also newly identified. We thus designated the longer and shorter transcripts as NAIPl and NAIPs, respectively. The cDNA clones for NAIPl and NAIPs should facilitate the functional analysis of the NAIP gene and its association with neuronal apoptosis and SMA.

Base Sequence↗