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Biomedical subjects

H Sakai

Publications and source records attributed to H Sakai.

At least 325 records · Page 18Linked to original sources
PubMed1999

Polymorphism of the endoglin gene in patients with intracranial saccular aneurysms.

OBJECT: Endoglin, a transforming growth factor beta-binding protein, is a glycoprotein expressed on the surface of human vascular endothelial cells. Mutations of this gene are responsible for hereditary hemorrhagic telangiectasis and are associated with sporadic intracerebral hemorrhage as a risk factor. The purpose of this study was to examine the polymorphism of this gene in patients with intracranial aneurysms. METHODS: The authors identified the mutations and insertion polymorphism around exon 7 of the endoglin gene in 82 patients with intracranial saccular aneurysms (aneurysm group) and 114 control volunteers (control group). A 6-base insertion (GGGGGA) was found in intron 7 at 26 bases beyond the 3' end of exon 7. The homozygous insertion of intron 7 of the gene was present in 20.7% of the aneurysm group compared with 6.1% of the control group (chi2 = 9.837, p = 0.0073). The insertion allele frequency was significantly higher in the aneurysm group (67 [40.8%] of 164) than that in the control group (63 [27.6%] of 228) (chi2 = 7.48, p = 0.0062). The most notable clinical characteristic of the 17 patients with homozygous insertion in the aneurysm group was the relatively high percentage of patients with hypertension and of those with multiple aneurysms. CONCLUSIONS: The data provide evidence of an association between aneurysm development and a polymorphism at a genetic variant of endoglin in patients with these lesions.

Adult↗
PubMed1999

Respiratory impedance during positive expiratory airway pressure in patients with chronic obstructive pulmonary disease.

The effect of positive airway pressure (5.0 hPa) on airway impedance (Za) and tissue impedance (Zt) during the expiratory phase in chronic obstructive pulmonary disease (COPD) patients was evaluated using random noise oscillation and a body box method. The results were then compared with those obtained from normal subjects. In normal subjects, there was no significant difference between non-expiratory positive pressure (NPEP) and positive expiratory pressure (PEP) for the Zar (real part) and Zai (imaginary part) at 10 Hz (Zar NPEP: 2.14 +/- 0.76, PEP: 1.96 +/- 0.79; Zai NPEP: 1.42 +/- 0.66, PEP: 1.40 +/- 0.70 hPa l-1 s). However, in COPD patients, Zar decreased significantly and the Zai increased significantly during PEP as compared to the values during NPEP (Zar NPEP: 7.10 +/- 1.88, PEP: 5.97 +/- 1.67, P < 0.05; Zai NPEP: -4.10 +/- 2.27, PEP: -2.99 +/- 2.62 hPa l-1 s, P < 0.05). These results suggested that both central and peripheral airway resistance decreased during PEP in COPD patients. Tissue compliance (Ct) calculated from the Zt increased significantly during PEP as compared to during NPEP, in both normal subjects and in COPD patients (normal NPEP: 0.024 +/- 0.004, PEP: 0.021 +/- 0.003, P < 0.05; COPD NPEP: 0.024 +/- 0.004, PEP: 0.014 +/- 0.004 l hPa-1, P < 0.001). This may have been indicative of the stiffened chest wall during PEP.

Adult↗
PubMed1999

A circle map model of human circadian rhythms.

Peculiar relationships between the sleep-wake cycle and temperature rhythm have been found during free-run situations, i.e. internal synchronization, internal desynchronization and phase trapping. The periods of both rhythms and the phase relationships between them could well characterize the above behavioral states. In this paper, firstly, our mathematical interpretations for them are proposed. According to these interpretations, a new circadian system model is developed. Our model consists of two circle maps, one for the dynamics of sleep-onset phase and the other wake-onset phase in reference to the temperature rhythm. The model dynamics is controlled mainly by the map for sleep-onsets which simultaneously determines behavior of wake-onsets. The model parameters are uniquely estimated based on the experimental results. The diverse behavior of the sleep-wake cycle associated with the synchronized and desynchronized states is suggested to be understood as bifurcation phenomena of the model dynamics. The bifurcation of the model dynamics is controlled by a single parameter, whose quantitative characteristics are investigated in detail. The results shown here could provide a novel framework to understand the human circadian rhythms systematically.

Body Temperature↗
PubMed1999

[Measurements and clinical usefulness of carboxyterminal propeptide of type I collagen and cross-linked carboxyterminal telopeptide of type I collagen in patients with prostate cancer].

Carboxyterminal propeptide of type I collagen (P1CP) and cross-linked carboxyterminal telopeptide of type I collagen (1CTP) are known as parameters of bone metastasis in patients with prostate cancer (PCa). We measured the serum P1CP and 1CTP levels in 52 PCa patients and evaluated the clinical usefulness of these serum markers. Both serum levels of P1CP and 1CTP were significantly higher in patients with extent of disease (EOD) grade 2 or 3 bone metastases than in patients without bone metastasis. Thus, P1CP and 1CTP are not as useful at first detection of bone metastases as bone scintigram. On the other hand, in the patients who indicated high serum levels of P1CP or 1CTP before initial treatment, the changes in the concentrations of these markers may be helpful in evaluating the response to treatment or the progression of disease. Our results suggest that P1CP and 1CTP are useful markers for monitoring the metastatic burden in the bone of PCa patients, but the efficacy is limited in high EOD grade cases.

Aged↗
PubMed1999

[Two cases of an intracranial large hemangiopericytoma associated with brain swelling in the early operative stage].

Intracranial hemangiopericytomas are hypervascular tumors. Consequently, resection of these tumors must occasionally be stopped owing to profuse bleeding. We report two cases of large intracranial hemangiopericytoma whose resection had to be stopped owing not to bleeding but to brain swelling. These patients were treated with large doses of barbiturate until the intracranial pressure had normalized. After preoperative irradiation therapy, the residual tumors were easily removed without serious complications. We speculate that the brain tissue around a large hemangiopericytoma might be under ischemia because of long-standing compression and deviation of blood to the hypervascular tumor. A large amount of blood flowing into these brain tissues due to external and internal decompression inverts cerebral perfusion acutely from ischemia to hyperemia. The brain swelling in the early operative stage would be evoked by this "inverted cerebral hyperemia". We found that brain swelling is sometimes encountered during the resection of a large hemangiopericytoma even in the early operative stage. If swelling occurs, tumor resection should be stopped immediately and intracranial pressure should be controlled. The residual tumor can then be easily removed without complications after preoperative irradiation therapy.

Adult↗
PubMed1999

Carbonyl stress: increased carbonyl modification of tissue and cellular proteins in uremia.

Advanced glycation end-products (AGEs) are formed during non enzymatic glycation and oxidation (glycoxidation) reactions. This process is accelerated in diabetics owing to hyperglycemia, and it has been implicated in the pathogenesis of diabetic complications. Surprisingly, AGEs increase in normoglycemic uremic patients to a much greater extent than in diabetics. AGE accumulation in uremia cannot be attributed to hyperglycemia nor simply to a decreased removal by glomerular filtration. Recently gathered evidence has suggested that, in uremia, the increased carbonyl compounds derived from carbohydrates and lipids modify proteins not only by glycoxidation reaction but also by lipoxidation reaction ("carbonyl stress"). Carbonyl stress has been implicated in the pathogenesis of long-term uremic complications such as dialysis-related amyloidosis. With regard to continuous ambulatory peritoneal dialysis (CAPD), the peritoneal cavity appears to be in a state of severe overload of carbonyl compounds derived from CAPD solution containing high glucose, from heat sterilization of the solution, and from uremic circulation. Carbonyl stress might modify not only peritoneal matrix proteins and alter their structures, but also react with mesothelial and endothelial cell surface proteins and initiate a range of inflammatory responses. Carbonyl stress might therefore contribute to the development of peritoneal sclerosis in patients with long-term CAPD.

Aldehydes↗
PubMed1999

Beta2-microglobulin and renal bone disease.

Dialysis-related amyloidosis (DRA) is characterized by amyloid deposition mainly in bone and joint structures, presenting as carpal tunnel syndrome, destructive arthropathy, and subchondral bone erosions and cysts. Beta2-microglobulin has been demonstrated to be a major constituent of amyloid fibrils. DRA occurs not only in patients undergoing long-term hemodialysis, but also in patients undergoing continuous ambulatory peritoneal dialysis. The incidence of this complication increases with the duration of dialytic therapy and the age of the patient. While a definitive diagnosis of DRA can be made only by histological findings, various imaging techniques often support diagnosis. The molecular pathogenesis of this complication remains unknown. Recent studies have, however, suggested a pathogenic role of a new modification of beta2-microglobulin in amyloid fibrils--that is, the advanced glycation end-products (AGEs) formed with carbonyl compounds derived from autoxidation of both carbohydrates and lipids ("carbonyl stress"). Therapy for DRA is limited to symptomatic approaches and surgical removal of amyloid deposits. High-flux biocompatible dialysis membranes could be used to delay DRA development.

Amyloid↗
PubMed1999

Successful low-dose cytosine arabinoside treatment in a patient with acute leukemia from idiopathic myelofibrosis.

We report a 63-year-old male with acute leukemia developed from idiopathic myelofibrosis. Cytogenetic analysis revealed chromosomal abnormalities; 46,XY,t(3;21)(q21;q22) del(20q). Intensive chemotherapies [combination of adriamycine/vincristine/prednisolone, or idarubicine/cytosine arabinoside (Ara-C)] were unsuccessful. The patient was then treated with continuous intravenous low-dose Ara-C because of his poor physical condition and showed marked hematological improvement. Leukemic cells disappeared from the peripheral blood and the segmented neutrophil count recovered. The dysplastic morphology observed in the segmented neutrophils suggests that the recovery of the neutrophils has resulted mainly from the differentiation activity of Ara-C.

Acute Disease↗
PubMed1999

[Endovascular surgery for untreated ruptured aneurysm with symptomatic vasospasm].

It is difficult to treat ruptured aneurysms with symptomatic vasospasm. Although direct surgery for such cases is associated with poor outcomes, conservative therapy has the risk of both rerupture and infarction. In two cases of ruptured aneurysms with symptomatic vasospasm, we performed aneurysmal coil embolization with Guglielmi electrodetatchable coils (GDC). At the same time we performed percutaneous transluminal angioplasty (PTA) with papaverine infusion. In both cases, rerupture did not occur and PTA was effective angiographically. A good outcome was achieved in case 1. However, broad cerebral infarction occurred in case 2, in which the patient had shown severe symptomatic vasospasm on admission. In advanced cases, such as in case 2, the outcome is poor. The aneurysm may not be able to be approached before PTA because of severe vasospasm. In such cases, PTA must be performed carefully to avoid aneurysmal rerupture. Intraarterial papaverine infusion is safer than PTA for severe spasm in distal vessels. However the efficacy of papaverine is known to be transient in many cases. It is often difficult to determine the exact relationship between branches and the aneurysm in the presence of vasospasm. In such cases, we recommend that the rupture point be packed and that the aneurysmal neck remain unpacked. After vasospasm is cured and good general condition has been recovered, direct surgery can be performed. In summary, endovascular surgery is an effective option for treatment of ruptured aneurysm with symptomatic vasospasm.

Aged↗
PubMed1999

A population-based, case-control study of Taenia solium taeniasis and cysticercosis.

A two-phase study was conducted in a rural community in Honduras, to evaluate the association between neurocysticercosis (NCC) diagnosed by computed tomography (CT), epilepsy, seropositivity for antibodies to the cysticerci of Taenia solium [determined by enzyme-linked-immunoelectrotransfer-blot (EITB) assays], intestinal infection with this parasite, and various epidemiological factors. Of the 480 individuals studied in the first phase, 17% were seropositive and 2.5% supplied faecal samples which contained T. solium eggs. In the second phase, 148 individuals (74 of the seropositive subjects from the first phase and 74 matched controls from the seronegatives) underwent CT and neurological examinations. The CT results appeared normal in 110 (74%) of the 148, showed anatomical abnormality in seven (5%), and active or calcified lesions compatible with NCC in 31 (23% of the seropositives and 19% of the seronegatives). Only five of the latter had neurological symptoms (two being epileptics) and only five lived in households in which intestinal taeniasis had been detected. Subject age was significantly associated with NCC-compatible lesions but all the other factors investigated, including seropositivity, showed no significant association with the CT findings. The overall sensitivity of the EITB assays was found to be 55%. Taken together, the present results indicate that, even though it is a valuable tool in determining transmission levels in sero-epidemiological studies, the EITB assay should not be used to predict the existence of NCC or to estimate the prevalence of NCC. The results do provide further evidence that taeniasis and cysticercosis are widely prevalent in Honduras, and indicate that much larger studies of hyper-endemic communities may be necessary if the factors associated with the transmission of T. solium are to be elucidated.

Adolescent↗
PubMed1999

Biochemical and physiological properties of pedicellarial lectins from the toxopneustid sea urchins.

Pedicellarial lectins (SUL-I, SUL-II, and TGL-I) were purified from the toxopneustid sea urchins, Toxopneustes pileolus and Tripneustes gratilla using gel filtration chromatography, affinity chromatography, and reverse-phase HPLC. SUL-I (Nakagawa et al., 1996) and SUL-II from the large globiferous pedicellariae of T. pileolus are D-galactose-binding lectins with molecular masses of 32 kDa and 23 kDa, respectively; while TGL-I from the globiferous pedicellariae of T. gratilla is a Ca(2+)-independent heparin-binding lectin with a molecular mass of 23 kDa. SUL-I induced mitogenic stimulation on murine splenocytes but TGL-I did not. At higher dose ranges SUL-I exhibited inhibitory effects on the cells. The dual response to SUL-I was effectively inhibited by D-galactose. SUL-I enhanced norepinephrine-induced contraction of isolated rat mesenteric artery with endothelium. When endothelium was removed from the artery, acetylcholine did not relax the norepinephrine-induced contraction. In the same artery the enhancing effect of the contraction by SUL-I was abolished, suggesting that SUL-I acts on the endothelium of mesenteric artery, and may release prostanoids. The present results suggest an extracellular function for SUL-I that may have wide-ranging effects in physiological processes. The primary role of pedicellarial lectins from T. pileolus and T. gratilla might be defense against a foreign body.

Agglutination↗
PubMed1999

Enhanced Ca2+ sensitization of the bronchial smooth muscle contraction in antigen-induced airway hyperresponsive rats.

To investigate the alteration in acetylcholine (ACh)-induced increase in Ca2+ sensitization of bronchial smooth muscle contraction concurrent with the airway hyperresponsiveness (AHR), the ACh-induced increases in cytosolic Ca2+ ([Ca2+]) level and contractile response were simultaneously determined by using Fura-2 loaded bronchial smooth muscle. The left main bronchi were isolated from AHR rats which were sensitized and repeatedly challenged with DNP-Ascaris antigen. The tissue ring preparations were incubated in loading solution containing 10 microM Fura-2AM for 3 hr at room temperature. Then the isometrical contraction and [Ca2+]i (F340/F380) were monitored. Although the ACh (10(-3) M)-induced contractile response in AHR group (322 +/- 60 % of 60 mM K+ induced contraction) was significantly greater than that in control animals (173 +/- 15 %, p<0.05), the ACh (10(-3) M)-induced increase in [Ca2+]i was without significant difference between the two groups (128 +/- 15 and 171 +/- 29% of 60 mM K+ -induced increase in [Ca2+]i, respectively). These findings suggest that an augmentation of ACh-induced Ca2+ sensitization may occur in bronchial smooth muscle of the rats with antigen-induced AHR.

Acetylcholine↗
PubMed1998

Unregulated exposure of the ribosomal M-site caused by NAC depletion results in delivery of non-secretory polypeptides to the Sec61 complex.

Nascent polypeptide associated complex (NAC) interacts with nascent polypeptides emerging from ribosomes. Both signal recognition particle (SRP) and NAC work together to ensure specificity in co-translational targeting by competing for binding to the ribosomal membrane attachment site. While SRP selects signal-containing ribosomes for targeting, NAC prevents targeting of signal peptide-less nascent chains to the endoplasmic reticulum membrane. Here we show that the ribosome binding that occurs in NAC's absence delivers signalless nascent chains to the Sec61 complex, underscoring the danger of unregulated exposure of the ribosomal M-site. Recently, the idea that NAC prevents ribosome binding has been challenged. By carefully examining the physiologic NAC concentration in a variety of tissues from different species we here demonstrate that the discrepancy resulted from subphysiologic NAC concentrations.

Animals↗
PubMed1998

Structures of membrane proteins determined at atomic resolution.

Following determination of the first crystal structure of the reaction center of Rhodopseudomonas viridis, a membrane protein, by X-ray crystal structure analysis at 3.0 A resolution, 18 X-ray crystal structures and two electron crystal structures of membrane proteins have been obtained at higher than 3.5 A resolution. Besides these integral membrane protein structures, three crystal structures of water-soluble proteins, which can enter membranes, have been determined by X-ray crystallography at high resolution. The structural features of membrane proteins have been summarized by inspecting these crystal structures. The polypeptide chain crosses the membrane in a helical conformation or a beta-strand. The central +10 A region of the transmembrane alpha-helix is dominated by hydrophobic residues. On both sides of the central region are concentrated polar aromatic residues. Charged residues are dominant around +15 A to +20 A. All the transmembrane beta-structures are found in pore-forming proteins. The central region of the transmembrane beta-structure is amphipathic with hydrophobic residues on the membrane exposed side. The distribution of amino acid residues on the membrane exposed surface of the transmembrane beta-structure is similar to that of the transmembrane alpha-helix. alpha-Helices anchoring the membrane surface region are amphipathic with hydrophobic residues inside and hydrophilic residues outside.

Animals↗
PubMed1998

Cyclic GMP-dependent cytoprotection against ethanol-induced damage in rabbit isolated gastric parietal cells.

Prostaglandin E2 stimulates a nitric oxide/cyclic GMP (NO/cGMP) pathway which activates basolateral Cl- channels in rabbit gastric parietal cells. We examined whether the NO/cGMP pathway protects parietal cells from ethanol (EtOH)-induced cytotoxicity, using a parietal cell-rich suspension purified from rabbit gastric mucosa. Cytotoxicity was assayed by measuring the release of a fluorescent dye from the cells. N2,O2-dibutyryl guanosine 3',5'-cyclic monophosphate (DBcGMP) showed a concentration-dependent protective effect against EtOH-induced cytotoxicity. The half-maximal effect of DBcGMP was observed at 24 microM. DBcGMP in a concentration-dependent manner opened the basolateral Cl- channels of parietal cells, the EC50 value being 44 microM. The EtOH-induced cytotoxicity decreased as the Cl- concentration of medium decreased. A 30-s treatment with 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), an inhibitor of the Cl- channel, had a cytotoxic effect which was not prevented by pre-incubation with DBcGMP. The cytotoxic effects of EtOH and NPPB were additive and the NPPB effects did not depend on the medium Cl- concentration. The present study showed that cGMP protects the gastric parietal cell from EtOH-induced cytotoxicity, and this cytoprotection is related to basolateral Cl- channel activity in the plasma membrane via an unknown mechanism(s).

Animals↗
PubMed1998

Protein kinase C-mediated up-regulation of Na+/Ca2+-exchanger in rat hepatocytes determined by a new Na+/Ca2+-exchanger inhibitor, KB-R7943.

The regulatory mechanism of the plasma membrane Na+/Ca2+-exchanger in isolated rat hepatocytes was studied using microspectrofluorometry and 45Ca2+ uptake methods. Exposure of single hepatocytes to low-Na+ solutions induced an increase in the intracellular Ca2+ concentration ([Ca2+]i) which depended on the presence of extracellular Ca2+. 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate (KB-R7943), a novel selective inhibitor of Na+/Ca2+-exchangers, inhibited the initial rate of [Ca2+]i increase induced by exposure to the low-Na+ solution (IC50 = 2 microM). KB-R7943 also reduced the initial rate of 45Ca2+ uptake (IC50 = 4 microM). The increase in [Ca2+]i induced by exposure to the low-Na+ solution was inhibited by pre-incubation with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7, 50 microM), but not with N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8, 60 microM) or a tyrosine kinase inhibitor, genistein (100 microM). Furthermore, taurocholate and phorbol-12,13-dibutyrate, both of which activate protein kinase C, promoted the increase in [Ca2+]i. These [Ca2+]i increases were sensitive to KB-R7943. Our results indicate that the Na+/Ca2+-exchanger is up-regulated via protein kinase C. The activity of Na+/Ca2+-exchangers is not evident under normal physiological conditions, suggesting that the exchanger may be activated under pathophysiological conditions.

Animals↗