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Biomedical subjects

H Sugimoto

Publications and source records attributed to H Sugimoto.

At least 91 records · Page 5Linked to original sources
PubMed2000

Effect of growth hormone on brain oedema caused by a cryogenic brain injury model in rats.

Although growth hormone (GH) is a potential agent to counteract the catabolic response to general and head injuries, the complications of GH treatment have been little studied. To evaluate the safety of GH in head trauma patients, it was investigated whether GH affects brain oedema caused by brain injury, using a rat freeze-injury model. Male Wistar rats (n = 28) were divided into four groups according to the substance injected (GH vs. saline) and whether brain was injured or not. GH (0.8 IU/kg) or saline was injected subcutaneously every 24 hours. In the injury groups, immediately before the first injection of GH, an aluminum rod cooled to -50 degrees C was placed on the right parietal region for 4 minutes, under anaesthesia. At 96 hours after the insult, brain and skeletal muscle were excised and their water content was measured, by drying. Freeze injury of the brain caused an increase in water content in skeletal muscle. GH injection augmented this oedema in skeletal muscle. Freeze injury of the brain also caused an increase in water content in the injured and non-injured hemispheres of brain and cerebellum. GH administration did not exacerbate brain oedema caused by brain injury in this model.

Animals↗
PubMed2000

Difference in the responses after administration of granulocyte colony-stimulating factor in septic patients with relative neutropenia.

OBJECTIVE: The objective of this study was to classify the clinical responses after administration of granulocyte colony-stimulating factor (G-CSF) in septic patients with relative neutropenia. PATIENTS AND METHODS: We administered recombinant human G-CSF (2 microg/kg) subcutaneously once a day for 5 days to 30 septic patients with white cell counts below 5,000 cells/mm3. Absolute neutrophil count (ANC), neutrophil differentiation, and serum concentration of G-CSF were determined serially. Bone marrow also was analyzed before and after treatment. RESULTS: Neutrophil responses to G-CSF varied from good (ANC > 10,000/mm3, group G, n = 20) to moderate (ANC < 10,000/mm3, group M, n = 5) to poor (no increase in ANC, group P, n = 5). Before G-CSF administration, the three groups showed no differences in ANC but did show significant differences in serum concentration of G-CSF. G-CSF concentration was 0.16 +/- 0.03 ng/mL in group G, 7.0 +/- 3.0 ng/mL in group M, and 270 +/- 90 ng/mL in group P. Immature neutrophils accounted for 35.0 +/- 3.7% of peripheral leukocytes in group P but only 5.1 +/- 0.6% in group G. Although bone marrow was depressed in all groups before G-CSF treatment, nucleated cell count increased significantly after rhG-CSF treatment in groups G and M. Survival rate after 4 weeks was 90% in group G and 100% in group M; no patient in group P survived. CONCLUSION: G-CSF administration was effective in septic patients with a low percentage of immature neutrophils and insufficient endogenous G-CSF. It had little effect on patients with a high percentage of immature neutrophils whose G-CSF production was up-regulated and whose bone marrow was severely depressed.

APACHE↗
PubMed2000

Half-life of blood carboxyhemoglobin after short-term and long-term exposure to carbon monoxide.

BACKGROUND: In models of smoke inhalation injury and carbon monoxide poisoning blood carboxy-hemoglobin (COHb) levels decrease faster than predicted by the generally recognized half-life of COHb. We studied the effects of duration of exposure to carbon monoxide (CO) on the subsequent CO elimination. METHODS: Each of four sheep were insufflated with CO gas mixtures either for a few minutes (short-term exposure) or for several hours (long-term exposure), then ventilated with air for 3 hours. Serial COHb concentrations were analyzed by using a two-compartment, single central outlet mathematical model. RESULTS: Short-term exposures exhibited biphasic decreases of COHb concentration compatible with a two-compartment model; an initial rapid decrease (half-life 5.7 +/- 1.4 minutes) was followed by a slower phase (103 +/- 20.5 minutes). Long-term exposures exhibited almost monophasic decreases, which were nevertheless compatible with the model (half-life, 21.5 +/- 2.1 and 118 +/- 11.2 minutes). CONCLUSION: This study demonstrated different patterns of CO elimination curve, which suggests distribution of CO to two compartments having different rates of equilibration.

Administration, Inhalation↗
PubMed2000

Characteristics of infection and leukocyte count in severely head-injured patients treated with mild hypothermia.

OBJECTIVE: This study was designed to characterize the infectious complications and kinetics of leukocyte count in severely head-injured patients treated with mild hypothermia. PATIENTS AND METHODS: We retrospectively analyzed the incidence and severity of infectious complications as well as daily changes in leukocyte count in 41 severely head-injured patients treated with mild hypothermia (group H). They were retrospectively compared with 25 severely head-injured patients treated with high-dose barbiturates (group B) and to 25 other severely head-injured patients treated with no barbiturates (group N). RESULTS: Initial intracranial pressure was significantly higher in group H than in the other groups. No significant differences existed in the incidence of pneumonia or meningitis among the three groups, whereas the incidence of bacteremia was significantly higher in group H than in the other two groups. Pneumonia was significantly more severe in group H than in the other groups. In six patients of group H, pneumonia spread fulminantly to become life threatening. Daily changes in total leukocyte count showed the same pattern, consisting of a peak, a nadir, and a second peak in all groups. Total leukocyte count was, however, significantly lower during the first 2 weeks in group H than in the other two groups. Lymphocyte and neutrophil counts were also lower in group H. CONCLUSION: Infectious complications were more severe and leukocyte counts were lower in patients treated with mild hypothermia, who also had the highest initial intracranial pressures, than in patients treated with conventional therapies. Measures against increased susceptibility to infection and leukocyte suppression should be explored.

Abbreviated Injury Scale↗
PubMed2000

Interleukin-1beta alters the oxygen delivery-oxygen consumption relationship in rabbits by increasing the slope of the supply-independent line.

When systemic oxygen delivery (DO2) is reduced, oxygen consumption (VO2) is maintained until a critical level is reached (DO2crit). Sepsis is thought to shift DO2crit to the right and lengthen the supply-dependent portion. We tested the effect of interleukin (IL)-1beta, which is one of the key cytokines related to sepsis, on the DO2-VO2 relationship. Fifteen rabbits were subjected to stepwise cardiac tamponade to reduce DO2 to 10% by inflating a handmade balloon placed into the pericardial sac. Seven rabbits were given 10 microg/kg of IL-1beta intravenously (IL-1beta group) prior to the graded cardiac tamponade. The remainder received saline alone (control group). The DO2-VO2 relationship was analyzed by the dual-line method. IL-1beta significantly decreased mean arterial pressure (65 +/- 11 mmHg from baseline 85 +/- 7 mmHg) without altering cardiac output. The IL-1beta group showed significantly steeper supply-independent line slopes than did the control group (0.19 +/- 0.02 vs. 0.11 +/- 0.02, respectively), which resulted in a DO2crit shift to the left (IL-1beta group, 8.7 +/- 1.7 ml/kg x min vs. control, 11.7 +/- 0.7 ml/kg x min). The IL-1beta group also showed greater PO2 and plasma lactate levels in the portal vein than did the control group. These results indicate that IL-1beta impairs systemic oxygen uptake even before VO2 becomes supply-dependent, presumably due to maldistribution of the blood flow including the splanchnic circulation.

Animals↗
PubMed2000

Identification of amino acids of influenza virus HA responsible for resistance to a fusion inhibitor, Stachyflin.

We have recently described a novel hemagglutinin (HA) conformational change inhibitor of human influenza virus, Stachyflin (Yoshimoto et al, Arch. Virol., 144, 1-14, 1999). Stachyflin-resistant variants of human influenza A/WSN/33 (H1N1) virus were isolated in vitro and the nucleotide sequences of their HA genes were determined. The relation of amino acid substitutions and Stachyflin resistance was analyzed with in vitro membrane fusion between HA-expressing cells and octadecylrhodamine (R18)-labelled chick erythrocytes (RBC). The amino acid substitutions, lysine to arginine at position 51 or lysine to glutamic acid at position 121 of the HA2 subunit of the HA protein was enough to confer a Stachyflin-resistant phenotype of HA protein. The molecular mechanism of anti-HA conformational change activity of Stachyflin is discussed.

Amino Acid Substitution↗
PubMed2000

Early-stage rheumatoid arthritis: prospective study of the effectiveness of MR imaging for diagnosis.

PURPOSE: To assess the effectiveness of magnetic resonance (MR) imaging for the diagnosis of early-stage rheumatoid arthritis (RA). MATERIALS AND METHODS: Fifty subjects (nine men and 41 women) with polyarthralgia who were suspected of having early-stage RA on the basis of clinical and radiographic findings were selected to undergo gadolinium-enhanced MR imaging of the hands. The MR imaging criterion for the diagnosis of early RA was bilateral enhancement in both wrists and/or the metacarpophalangeal and/or proximal interphalangeal joints. Follow-up continued until a final diagnosis was determined. Two patients left the study before the end of follow-up. RESULTS: Final diagnoses were established after a mean follow-up of 776 days: rheumatoid arthritis in 26 patients and nonrheumatoid disease in 22. Use of the MR imaging criterion yielded the correct diagnosis in 25 patients with RA and three false-positive results in three patients without RA. As compared with the traditional format and classification tree criteria of the American Rheumatism Association, the MR imaging criterion allowed detection of seven and six additional patients with true RA, respectively. CONCLUSION: The introduction of MR imaging into the diagnostic criteria for early RA may contribute to more accurate diagnosis in patients suspected of having RA and thus allow an earlier decision to start proper medication.

Adult↗
PubMed2000

Is color-flow duplex a good diagnostic test for detection of isolated calf vein thrombosis in high-risk patients?

Color-flow duplex scanning (CDS) is a good diagnostic test for lower extremity proximal deep vein thrombosis (DVT). This report aims to evaluate the diagnostic accuracy of CDS in detecting isolated calf DVT in two in-hospital populations. A total of 166 patients had routine DVT testing with both CDS and venography: 99 total joint arthroplasty patients and 67 symptomatic in-hospital patients. Isolated calf DVT was noted in 34% of arthroplasty patients and 12% of symptomatic in-hospital patients. Peroneal DVT was most common. The sensitivity, specificity, positive predictive value, and negative predictive value (with 95% confidence interval [CI]) of CDS in detecting isolated calf DVT in the symptomatic in-hospital group was 39% (16%-62%), 98% (94%-99%), 88% (65%-99%), and 81% (71%-91%), respectively. In the arthroplasty patients these values were 13% (3%-23%), 92% (85%-99%), 60% (30%-90%), and 55% (45%-65%), respectively. CDS has a low sensitivity in detecting isolated calf DVT among hospitalized patients and cannot be deemed an effective tool for identifying clots limited to only one or two tibial vessels.

Arthroplasty, Replacement, Hip↗
PubMed2000

Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma.

Omega-3 polyunsaturated fatty acids have anti-inflammatory effects in vitro, and high dietary levels are associated with a lower incidence of inflammatory diseases. However, only limited effects have been demonstrated in asthma. The effects of dietary supplementation with fish oil for 10 months in 29 children with bronchial asthma was investigated in a randomized controlled fashion. In order to minimize the effects of environmental inhaled allergens and diet, this study was performed in a long-term treatment hospital. Subjects received fish oil capsules containing 84 mg eicosapentaenoic acid (EPA) and 36 mg docosahexaenoic acid (DHA) or control capsules containing 300 mg olive oil. The daily dosages of EPA and DHA were 17.0-26.8 and 7.3-11.5 mg x kg body weight(-1), respectively. Asthma symptom scores decreased and responsiveness to acetylcholine decreased in the fish oil group but not in the control group. In addition, plasma EPA levels increased significantly only in the fish oil group (p<0.0088). No significant side-effects were observed. The present results suggest that dietary supplementation with fish oil rich in the omega-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid is beneficial for children with bronchial asthma in a strictly controlled environment in terms of inhalant allergens and diet.

Acetylcholine↗
PubMed2000

Development of anti-influenza drugs: II. Improvement of oral and intranasal absorption and the anti-influenza activity of stachyflin derivatives.

The in-vivo anti-influenza-virus activity of Stachyflin derivatives (III and its phosphate ester, III-Phos), a new class of haemagglutinin fusion inhibitor, and the improvement of their absorption after oral or intranasal administration were studied in mice, rats, and ferrets. The absorption of III in PEG 4000 and III-Phos aqueous solution increased about three and four fold in AUC after oral administration to uninfected mice compared with that of 0.5% HPMC (hydroxypropyl-methylcellulose) suspension. Using a mouse influenza virus infection model, significant anti-influenza-virus activity was observed in infected mice treated orally with these compounds dissolved in PEG 4000 or distilled water, respectively, but not in mice treated with 0.5% HPMC. The in-vivo anti-influenza-virus activity in ferrets, a good model for influenza virus infection in man, was also studied. Although the concentration of III in plasma was above the IC50 against the influenza virus strain used for 6h after the oral administration of III in PEG 400 to uninfected ferrets, no in-vivo anti-influenza-virus activity was observed at the same dosage given 4 times daily for 3 days. The intranasal administration of III-Phos, which was expected to have a more notable in-vivo anti-influenza-virus activity, was examined. III-Phos, whose intranasal absorption had been improved by the modification of III with phosphate ester in rats, inhibited viral replication in the nasal cavity and suppressed influenza-virus-induced fever when administered intranasally to infected ferrets. This study demonstrates that intranasally administered compounds with anti-influenza-virus activity must permeate the nasal membranes to produce their anti-influenza-virus effect.

Absorption↗
PubMed2000

Studies on the constituents of Broussonetia species. VII. Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, as inhibitors of glycosidase, from Broussonetia kazinoki SIEB.

Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, were isolated from the branches of Broussonetia kazinoki SIEB, (Moraceae). Broussonetines M, O, P, and Q were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(10S)-10,13-dihydroxy-tri decyl]pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)9-oxo-13-hydroxy-3- tridecenyl]pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)10-oxo-13-hydroxy-3-++ +tridecenyl]pyrrolidine (3), and (2R,3S,4R,5R)-2-hydroxymethyl-3-hydroxy-4-(beta-D-glucopyranosyloxy++ +)-5-[10-oxo-13-(beta-D-glucopyranosyloxy)tridecyl]pyrrolidine (4) respectively, by spectroscopic and chemical methods. 1-4 inhibited beta-glucosidase, beta-galactosidase and beta-mannosidase.

Alkaloids↗
PubMed2000

Structural features of N-glycans linked to royal jelly glycoproteins: structures of high-mannose type, hybrid type, and biantennary type glycans.

The structures of N-glycans of total glycoproteins in royal jelly have been explored to clarify whether antigenic N-glycans occur in the famous health food. The structural feature of N-glycans linked to glycoproteins in royal jelly was first characterized by immunoblotting with an antiserum against plant complex type N-glycan and lectin-blotting with Con A and WGA. For the detail structural analysis of such N-glycans, the pyridylaminated (PA-) N-glycans were prepared from hydrazinolysates of total glycoproteins in royal jelly and each PA-sugar chain was purified by reverse-phase HPLC and size-fractionation HPLC. Each structure of the PA-sugar chains purified was identified by the combination of two-dimensional PA-sugar chain mapping, ESI-MS and MS/MS analyses, sequential exoglycosidase digestions, and 500 MHz 1H-NMR spectrometry. The immunoblotting and lectinblotting analyses preliminarily suggested the absence of antigenic N-glycan bearing beta1-2 xylosyl and/or alpha1-3 fucosyl residue(s) and occurrence of beta1-4GlcNAc residue in the insect glycoproteins. The detailed structural analysis of N-glycans of total royal jelly glycoproteins revealed that the antigenic N-glycans do not occur but the typical high mannose-type structure (Man(9 to approximately 4)GlcNAc2) occupies 71.6% of total N-glycan, biantennary-type structures (GlcNAc2Man3 GlcNAc2) 8.4%, and hybrid type structure (GlcNAc1 Man4GlcNAc2) 3.0%. Although the complete structures of the remaining 17% N-glycans; C4, (HexNAc3 Hex3HexNAc2: 3.0%), D2 (HexNAc2Hex5HexNAc2: 4.5%), and D3 (HexNAc3Hex4HexNAc2: 9.5%) are still obscure so far, ESI-MS analysis, exoglycosidase digestions by two kinds of beta-N-acetylglucosaminidase, and WGA blotting suggested that these N-glycans might bear a beta1-4 linkage N-acetylglucosaminyl residue.

Blotting, Western↗
PubMed2000

Donepezil hydrochloride (E2020) and other acetylcholinesterase inhibitors.

A wide range of evidence shows that acetylcholinesterase (AChE) inhibitors can interfere with the progression of Alzheimer's disease (AD). The successful development of these compounds was based on a well-accepted theory that the decline in cognitive and mental functions associated with AD is related to the loss of cortical cholinergic neurotransmission. The earliest known AChE inhibitors, namely, physostigmine and tacrine, showed modest improvement in the cognitive function of Alzheimer's patients. However, clinical studies show that physostigmine has poor oral activity, brain penetration and pharmacokinetic parameters while tacrine has hepatotoxic liability. Studies were then focused on finding a new type of acetylcholinesterase inhibitor that would overcome the disadvantages of these two compounds. Donepezil hydrochloride inaugurates a new class of AChE inhibitors with longer and more selective action with manageable adverse effects. Currently, there are about 19 new Alzheimer's drugs in various phases of clinical development.

Alzheimer Disease↗
PubMed2000

[The clinical study on KL-6 and SP-D in sera of patients with various pulmonary diseases].

It has been reported that serum levels of KL-6 and surfactant protein D(SP-D) can be useful indicators for interstitial pneumonia(IP). In the present study, we evaluated the clinical significance of KL-6 and SP-D by measuring the serum levels of patients with various pulmonary diseases by enzyme-linked immunosorbent assay. Serum levels of KL-6 in patients with idiopathic interstitial pneumonia(IIP), collagen disease with interstitial pneumonia(CDIP), lung cancer(LC) and LC with idiopathic interstitial pneumonia were significantly higher than of those in healthy controls. Moreover, serum levels of KL-6 were significantly higher in patients with active IP than in those with inactive IP. Serum levels of SP-D in patients with IIP and CDIP were significantly higher than of those in healthy controls. When a cut-off level of KL-6 or SP-D in sera was defined as a value of healthy controls representing the means + 2SD, the serum KL-6 positive diagnostic rate for IP(79.2%) was higher than that of SP-D(66.7%). The SP-D positive diagnostic rate for lung diseases other than IP(11.6%) was lower than that of KL-6(34.9%). The serum concentration of KL-6 in patients with the pulmonary diseases significantly correlated with that of SP-D. These findings suggest that KL-6 may be superior in the sensitivity of IP and can be used to evaluate the disease activity of IP. In addition, SP-D may be more specific for IP than KL-6.

Aged↗
PubMed2000

[Estimation of age from teeth using the racemization of aspartic acid (racemization method)].

We report a method for estimation of age from teeth using the racemization of amino acids (racemization method). This method is based on the characteristics of the constant age-related increase in the amount of D-aspartic acid in dentin. We estimated age by measuring the ratio of D-aspartic acid to L-aspartic acid, i.e. the ratio of racemization ¿ratio of D/L, ln[(1 + D/L)/(1 - D/L)]¿. Because different D/L ratios have been obtained from different teeth in the same individuals and from different sites of dentin in the same tooth, we usually prepare bucco-lingual longitudinal sections at the central part of each tooth, and prepare samples of powdered whole dentin. This powder is then mixed and used to measure the D/L ratio in the dentin. To accurately estimate age from forensic specimens, we simultaneously measured the D/L ratios in more than four control teeth of the same type obtained from subjects of known age. Use of control teeth is necessary because it is sometimes difficult to maintain constant running conditions for gas chromatography to obtain reproducible values in different runs. Therefore, for every measurement, we determined an equation for calculating age from the D/L ratios of control teeth, and estimated the age of the specimen tooth by substituting in its D/L ratio. The most reliable results were obtained using samples of lower incisors or premolars, which are single-rooted teeth with a relatively small volume of dentin. Thus sampling of the dentin is easier than for other teeth. It is better to keep control teeth desiccated because racemization does not proceed readily under such conditions. The deviation from the actual age in the cases we examined was less than 3 years. Thus, racemization of amino acids can be used for accurate estimation of age from teeth.

Adolescent↗
PubMed1999

Observation of Multi-TeV Gamma Rays from the Crab Nebula using the Tibet Air Shower Array.

The Tibet experiment, operating at Yangbajing (4300 m above sea level), is the lowest energy air shower array, and the new high-density array constructed in 1996 is sensitive to gamma-ray air showers at energies as low as 3 TeV. With this new array, the Crab Nebula was observed in multi-TeV gamma-rays and a signal was detected at the 5.5 sigma level. We also obtained the energy spectrum of gamma-rays in the energy region above 3 TeV which partially overlaps those observed with imaging atmospheric Cerenkov telescopes. The Crab spectrum observed in this energy region can be represented by the power-law fit dJ&parl0;E&parr0;&solm0;dE=&parl0;4.61+/-0.90&parr0;x10-12&parl0;E&solm0;3 TeV&parr0;-2.62+/-0.17 cm-2 s-1 TeV-1. This is the first observation of gamma-ray signals from point sources with a conventional air shower array using scintillation detectors.

Journal Article↗
PubMed1999

Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: a platform for antiviral drug design.

HIV integrase, the enzyme that inserts the viral DNA into the host chromosome, has no mammalian counterpart, making it an attractive target for antiviral drug design. As one of the three enzymes produced by HIV, it can be expected that inhibitors of this enzyme will complement the therapeutic use of HIV protease and reverse transcriptase inhibitors. We have determined the structure of a complex of the HIV-1 integrase core domain with a novel inhibitor, 5ClTEP, 1-(5-chloroindol-3-yl)-3-hydroxy-3-(2H-tetrazol-5-yl)-pro penone, to 2.1-A resolution. The inhibitor binds centrally in the active site of the integrase and makes a number of close contacts with the protein. Only minor changes in the protein accompany inhibitor binding. This inhibitor complex will provide a platform for structure-based design of an additional class of inhibitors for antiviral therapy.

Binding Sites↗