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S Saito

Publications and source records attributed to S Saito.

At least 145 records · Page 8Linked to original sources

Effects of small doses of prostaglandin E(1) on systemic hemodynamics and jugular venous oxygen saturation during cardiopulmonary bypass.

STUDY OBJECTIVE: To examine the effects of small doses of prostaglandin E(1) (PGE(1)) on systemic hemodynamics and cerebral oxygenation during cardiopulmonary bypass(CPB). DESIGN: Randomized, prospective study. SETTING: Cardiac surgery at Saitama Cardiovascular and Pulmonary Center. PATIENTS: Forty patients who underwent elective coronary artery bypass surgery. INTERVENTIONS: The study was performed at the stable CPB period. Patients were randomly divided into four groups: control group (n = 10) received an infusion of saline, PGE(1) 10 group (n = 10) received an infusion of PGE(1) 10 ng/kg/min, PGE(1) 25 group (n = 10) received an infusion of PGE(1) 25 ng/kg/min, and the PGE(1) 50 group (n = 10) received an infusion of PGE(1) 50 ng/kg/min. MEASUREMENTS: After measuring the baseline partial pressure of the arterial oxygen saturation (SpO(2)), mixed venous oxygen saturation (SvO(2)), and jugular venous oxygen saturation (SjvO(2)), blood gases, and cardiovascular hemodynamic values, PGE(1) was infused intravenously at rate of between 10 and 50 ng/kg/min. PGE(1) infusion continued 30 minutes after the start of drug infusion, and the blood gas analysis and cardiovascular hemodynamic values were simultaneously determined together with the hemodynamic values at 2, 5, 10, 20, and 30 minutes during drug infusion. At 30 minutes after discontinuation of the drug infusion, the blood gas analyses were simultaneously determined together with the hemodynamic values. MAIN RESULTS: Mean arterial pressure (MAP) in PGE(1) 25 and 50 groups was decreased 20 and 30 minutes after the start of PGE(1) infusion compared with the baseline value (p < 0.05). In contrast, SvOm(2) in PGE(1) 25 and 50 groups was increased 20 and 30 minutes after the start of PGE(1) infusion compared with the baseline value (p < 0.05). There was no change in SjO(2) value despite a decrease in MAP during the study. CONCLUSIONS: Cerebral oxygenation estimated by SjvO(2) was maintained despite a decrease in MAP during the administration rate of PGE(1) between 10 and 50 ng/kg/min.

Aged↗

Reliable long-term non-pulsatile circulatory support without anticoagulation.

OBJECTIVE: The Terumo implantable left ventricular assist system (T-ILVAS) consists of a titanium centrifugal pump with a unique magnetically suspended impeller producing continuous (non-pulsatile) flow up to 10 l/min. The interior surface is heparin-coated and there is no purge system. We implanted the device into six sheep to ascertain in-vivo haemodynamic function, mechanical reliability and biocompatibility. METHODS: The T-ILVAS was implanted via left thoracotomy without cardiopulmonary bypass. The inflow cannula was placed in the left ventricular apex and a Dacron outflow graft anastomosed to the descending aorta. All animals recovered well. No anticoagulation (heparin or warfarin) was given after the surgery. Suspension position, motor current, impeller speed and pump flow were continuously monitored and stored by on-line computer. Serial blood samples were collected to determine haematological and biochemical indices of renal function, liver function and haemolysis. All animals were electively euthanized between 3 and 7 months postoperatively. The explanted pumps were examined for mechanical reliability and thrombus formation. Major organs were examined macroscopically and histologically for thromboembolism. RESULTS: All animals appeared completely normal for up to 210 days. At speeds between 1500 and 2000 rev./min the device pumped up to 8 l/min capturing all mitral flow. There were no major complications (pump failure, thromboembolism, haemorrhage, or driveline infection). Indices of haemolysis, liver and renal function remained within normal limits. All pumps were mechanically sound and free from thrombus. One embolus was found in a sectioned kidney. CONCLUSION: The T-ILVAS successfully supported the systemic circulation without anticoagulation for up to 210 days. Mechanical reliability and biocompatibility were demonstrated. Organ function remained within normal limits during continuous non-pulsatile flow.

Animals↗

Frequency-dependent electrophysiological effect of ibutilide on human atrium and ventricle.

Most of the class III antiarrhythmic agents developed in recent years blocks the rapid component of delayed rectifier potassium current (IKr). IKr blocker shows reverse use-dependency and also may cause torsades de pointes at slower heart rate. Ibutilide fumarate, a novel class III antiarrhythmic agent, increases window Na(+) current at the action potential plateau phase. We studied the rate-dependent effect of ibutilide on the electrophysiological parameters of human atrium and ventricle. Franz catheter and a pacing catheter were placed closely in the high right atrium and right ventricular apex to record monophasic action potentials (MAP) during pacing at cycle length (PCL) of 600 ms and 350 ms in eight patients who underwent electrophysiological study. MAP duration of right atrium (RA-MAPD) and right ventricle (RV-MAPD), effective refractory period of RA and RV (RA-ERP and RV-ERP), intra-atrial conduction time (IACT) and intra-ventricular conduction time (IVCT) were measured before and after intravenous administration of ibutilide (0.01 mg/kg up to 1mg). A conduction time from RA pacing spike to distal coronary sinus potential was used to measure IACT, while QRS duration of surface ECG during RV pacing was used to measure IVCT. Ibutilide prolonged RA-MAPD by 60 ms at PCL 600 ms and by 53 ms at PCL 350 ms; RV-MAPD by 48 ms at PCL 600 ms and by 55 ms at PCL 350 ms. Ibutilide did not affected RA and RV-ERP/MAPD ratio, IACT, and IVCT. Ibutilide prolongs MAPD and ERP of human atrium and ventricle without reverse use-dependency.

Action Potentials↗

Monoclonal antibody (5F3) defining renal cell carcinoma-associated antigen disialosyl globopentaosylceramide (V3NeuAcIV6NeuAcGb5), and distribution pattern of the antigen in tumor and normal tissues.

Renal cell carcinoma (RCC) has been characterized by high expression of three types of disialogangliosides: two based on lacto-series type 1 structure (disialosyl Lc(4), GalNAc disialosyl Lc(4)), the other based on globo-series structure (disialosyl globopentaosylceramide; disialosyl Gb5). The present study established a mAb, 5F3, directed to disialosyl Gb5. 5F3 was established after immunization with RCC cell line ACHN. The major disialoganglioside antigen isolated from ACHN cells, showing specific reactivity with 5F3, was characterized unequivocally as disialosyl Gb5 (V(3)NeuAcIV(6)NeuAcGb5) by identification of the core structure as globopentaosylceramide (Gb5) after enzymatic and acid hydrolysis, and by 2-dimensional (1)H-NMR spectroscopy. 5F3 does not react with monosialosyl Gb5 (V(3)NeuAcGb5), Gb5, or any lacto-series structures. 5F3 strongly stained 19 of 41 cases of primary RCC tissue. It reacted with proximal tubules (but not distal tubules) of kidney, microglial cells of cerebrum and cerebellum, goblet cells of stomach and intestine, smooth muscle of various organs. It did not react with parenchymatous cells of various organs, except for kidney epithelia and prostate stroma. Immunostaining of RCC tissue by mAb 5F3, in combination with staining by other antibodies directed to globo-series and lacto-series structures, has prognostic significance in defining metastatic potential of RCC.

Antibodies, Monoclonal↗

Herpes simplex virus in the vestibular ganglion and the geniculate ganglion-role of loose myelin.

This study presents the first direct evidence for herpes simplex virus type 1 (HSV-1) infection in the neurons of the vestibular ganglion. Although many investigators have reported electron microscopic evidence of HSV-1 infection in sensory ganglia, HSV-1 infection in the vestibular ganglion has not been described. Vestibular ganglion neurons have a unique structure, with a loose myelin sheath instead of the satellite cell sheath that is seen in other ganglia. This loose myelin is slightly different from compact myelin which is known as too tight for HSV-1 to penetrate. The role of loose myelin in terms of HSV-1 infection is completely unknown. Therefore, in an attempt to evaluate the role of loose myelin in HSV-1 infection, we looked for HSV-1 particles, or any effects mediated by HSV-1, in the vestibular ganglion as compared with the geniculate ganglion. At the light microscopic level, some neurons with vacuolar changes were observed, mainly in the distal portion of the vestibular ganglion where the communicating branch from the geniculate ganglion enters. At the electron microscopic level, vacuoles, dilated rough endoplasmic reticulum and Golgi vesicles occupied by virus were observed in both ganglia neurons. In contrast, viral infections in Schwann and satellite cells were observed only in the geniculate ganglion, but not in the vestibular ganglion. These results suggest that loose myelin is an important barrier to HSV-1 infection, and it must play an important role in the prevention of viral spread from infected neurons to other cells.

Animals↗

Time course of changes in jugular venous oxygen saturation during hypothermic or normothermic cardiopulmonary bypass in patients with diabetes mellitus.

BACKGROUND: Preexisting diabetic mellitus is a risk factor determining postoperative neurological disorders. The present study assesses the effects of normothermic and hypothermic cardiopulmonary bypass (CPB) on jugular venous oxygen saturation (SjvO2)in patients with preexisting diabetic mellitus. METHODS: Sixteen diabetic patients who underwent elective coronary artery bypass grafting surgery were randomly divided into two groups: Group DN (n=8, diabetic patients) underwent normothermic CPB (>35 degrees C), and group DH (n=8, diabetic patients) underwent hypothermic CPB (32 degrees C). Controls were 16 age-matched non-diabetic patients (normothemic group, CN: n=8; hypothemic group, CH: n=8). A 4.0 F fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor SjvO2 values. Hemodynamic parameters and arterial and jugular venous blood gases were measured seven times. RESULTS: Cerebral desaturation, which was defined as SjvO2 values below 50%, was observed during normothermic CPB in diabetic patients (at the onset of CPB: 46+/-3%, at 20 min after onset of CPB: 49+/-3%, means+/-SD, respectively). No cerebral desaturation occurred in diabetic and control patients during hypothermic CPB. CONCLUSIONS: Patients with preexisting diabetes mellitus experienced cerebral desaturation during normothermic CPB.

Aged↗

Effect of intravenous prostaglandin E1 on pial vessel diameters and intracranial pressure in rabbits.

BACKGROUND: The main advantages of prostaglandin E1 (PGE1) for induced hypotension during neurosurgery include a rapid onset of action, a quick recovery from hypotension, lack of toxicity, maintenance of adequate perfusion to vital organs, and maintenance of cerebral blood flow reactivity to carbon dioxide during hypotension. However, there is no report that shows the effect of PGE1 on cerebral microvessel diameter and only a few data are available that show the effect of PGE1 on intracranial pressure. The aim of this study was to measure cerebral arteriole and venule diameters and intracranial pressure (ICP) during PGE1-induced hypotension to evaluate whether PGE1 is suitable for neuroanesthesia. METHODS: We measured the effects of 0.1, 0.3, 1.0, 3.0, and 10.0 microg x kg(-1) x min(-1) of intravenous PGE1 on mean arterial pressure (MAP), cerebral arteriole and venule diameters and ICP in anesthetized rabbits. RESULTS: MAP decreased statistically significantly from baseline at the infusion rates of 1.0, 3.0, and 10.0 microg x kg(-1) x ml(-1). Arteriole diameter increased significantly from the baseline at the infusion rate of 10.0 microg x kg(-1) x ml(-1) (18% from control). Venule diameter did not change from baseline value at any infusion rate. ICP did not change from baseline value at any infusion rate. CONCLUSION: We conclude that PGE1 might be a suitable drug for induced hypotension in neurosurgery from the viewpoint of its small effect on the cerebral microvessels and ICP.

Alprostadil↗

Seasonal changes of humoral and cellular immune responses to Japanese cedar (Cryptomeria japonica) pollen allergens in Japanese monkeys (Macaca fuscata) with pollinosis.

The natural occurrence of Japanese cedar [Cryptomeria japonica (CJ)] pollinosis has been reported in Japanese monkeys (Macaca fuscata). The present study was designed to investigate seasonal changes in immunological reactions to CJ pollen allergens in monkeys with CJ pollinosis. Blood samples were collected from six monkeys with CJ pollinosis before and after CJ pollen season. Seasonal changes in specific IgE and IgG to major allergens (Cry j 1 and Cry j 2) were observed before and after CJ pollen season. The humoral responses decreased significantly before CJ pollen and increased after CJ pollen season. Similar seasonal changes in peripheral blood mononuclear cells proliferative responses to CJ allergens were observed before and after CJ pollen season. These humoral and cellular immune responses might serve as a biomarker for assessing new immunotherapies for monkeys with pollinosis.

Allergens↗

A novel surface molecule of Th2- and Tc2-type cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ T cells during the early stage of pregnancy.

It has been demonstrated that pregnancy induces the immunomodulation of cytokine responses away from the Th1 paradigm and towards the Th2 paradigm. In this study, we examined the expression of CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2) on decidual CD4+ and CD8+ T cells during the early stages of pregnancy. Examination of the cytokine profile revealed that CRTH2 was expressed on CD4+-type-2 T helper (Th2-type) and CD8+-type 2 T cytotoxic (Tc2-type) cells. The percentages of CRTH2+ cells in CD3+/CD4+ T cells and CD3+/CD8+ T cells were significantly higher in the decidua than in the peripheral blood. These results indicate the significance of Th2- and Tc2-type cells of the decidua in the maternal immune system, presumably through their production of cytokines which may contribute to the maintenance of pregnancy.

Adult↗

Disturbances in hepatocellular function during cardiopulmonary bypass using propofol anaesthesia.

BACKGROUND AND OBJECTIVE: Serum hyaluronate is thought to be an indicator of derangement in hepatocellular integrity, and the change in serum hyaluronate is a useful indicator in various liver disorders. We assessed the changes in serum hyaluronate in patients undergoing coronary artery bypass graft surgery. METHODS: Eleven patients scheduled for elective coronary artery bypass graft surgery were studied. An oximetry oxygen saturation catheter was inserted into the right hepatic vein to permit monitoring of hepatic venous oxygen saturation. Perioperative measurements included: haemodynamic variables; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; arterial and hepatic venous plasma concentrations of lactate, arterial ketone body ratio (ratio of acetoacetate to 3-hydroxybutyrate); and arterial and hepatic venous hyaluronate were measured. RESULTS: Arterial and hepatic venous hyaluronate increased during cardiopulmonary bypass compared with the prebypass period. These increases returned to prebypass values after the cessation of bypass (hepatic venous hyaluronate value at the prebypass period: 26 +/- 13 ng mL(-1), during bypass: 77 +/- 40 ng mL(-1); 1 h after bypass: 57 +/- 42 ng mL(-1); 6 h after bypass: 32 +/- 15 ng L(-1), 24 h after bypass; 62 +/- 21 ng mL(-1); mean +/- SD, P < 0.05). The arterial and hepatic venous hyaluronate during cardiopulmonary bypass was correlated with total bilirubin and hepatic venous lactate concentrations 6 h after bypass (arterial hyaluronate at cardiopulmonary bypass period vs. total bilirubin at 6 h after bypass; r=0.793, P=0.0036, hepatic venous hyaluronate during bypass vs. that at 6 h after bypass; r=0.795, P=0.0035). CONCLUSIONS: Hepatocellular integrity might be disturbed during cardiopulmonary bypass when propofol anaesthesia is used.

Alanine Transaminase↗

Sevoflurane and nitrous oxide anaesthesia suppresses heart rate variabilities during deliberate hypotension.

BACKGROUND AND OBJECTIVE: Despite the fact that both general anaesthetics and hypotensive drugs influence autonomic nervous activity, no study has yet examined the heart rate variability during deliberate hypotension and general anaesthesia. The aim of this was to clarify the heart rate variability changes during deliberate hypotension under sevoflurane-nitrous oxide anaesthesia. METHODS: Autonomic nervous system activity in patients (n=45) subjected to deliberate hypotension during sevoflurane in nitrous oxide and oxygen anaesthesia was investigated by a heart rate variability measurement. Three different types of hypotensive drugs, a calcium channel antagonist (nicardipine), a nitric oxide donor (nitroglycerin) and a vasodilatory prostaglandin (alprostadil), were used to induce hypotension. RESULTS: In all groups, low frequency power (sympathetic and parasympathetic indicator) and the ratio of low frequency to high frequency power (the LF/HF ratio, sympathetic indicator) were suppressed by induction of anaesthesia. In the control group, preanaesthesia low frequency power was 195 +/- 139 ms(2), the LF/HF ratio 10.3 +/- 5.7, during anaesthesia 5 +/- 9 ms(2), 0.6 +/- 0.8, respectively, P=0.0093, 0.0034, whereas high frequency power (parasympathetic indicator) was not significantly changed. In those patients receiving nicardipine or nitroglycerin during anaesthesia, these variables did not differ significantly from those in the control group. During prostaglandin E1 infusion, high frequency power was higher compared with the values in the other groups (17 +/- 12 ms(2) in the prostaglandin group, 7 +/- 6 ms(2) in the nicardipine group, 6 +/- 5 ms(2) in the nitroglycerin group and 6 +/- 4 ms(2) in the control group, respectively, P=0.0326, 0.0251, 0.0197). CONCLUSIONS: Sevoflurane in nitrous oxide and oxygen anaesthesia reduces sympathetic autonomic activity considerably, and the expected increases caused by hypotensive agents that occur in awake volunteers were not seen.

Alprostadil↗

Brachytherapy for prostate cancer in Japan.

The temporary implantation of iridium-192 (Ir-192) is available in Japan if the patient is isolated in a radiation control area during the treatment. In this study, brachytherapy for prostate cancer was preceded by using low-dose rate Ir-192. Twenty-six patients with localized prostate cancer were treated with brachytherapy since December 1997. The age of patients ranged from 61 to 82 (median 76) years and the initial serum prostate-specific antigen (PSA) level ranged from 4.3 to 141 (median 17.4) ng/ml. Ten to 14 needles with Teflon sheaths were introduced into the prostate via a transperineal approach and an Ir-192 wire was placed in each sheath. The dose-distribution curve based on computed tomography imaging was drawn and the irradiation time was calculated for the whole prostate to receive over 70 Gy. During the 1-22-month follow-up period, all cases with an initial PSA level of less than 25 ng/ml showed continuous PSA decrease without biochemical failure. Magnetic resonance imaging demonstrated tumor regression in all cases within 6 months after the treatment. One-year biopsy specimens from patients with PSA failure demonstrated viable tumor cells, and the specimens from patients with favorable progress revealed fibrosis replacement without any variable tumor cells. Characterization of nocturnal penile tumescence data and IIEF 15 score proved the minimal effect of the treatment on erectile function. No major side effects or complications were observed. Brachytherapy using Ir-192 is a less invasive and safe procedure, which is expected to become a standard treatment for localized prostate cancer patients with relatively low PSA levels.

Aged↗

A simple, inexpensive, life-saving way to perform iterative laparotomy in patients with severe intra-abdominal sepsis.

Between 1 June 1993 and 31 December 1998, 17 patients underwent temporary abdominal closure with 3L urological irrigation bags, because in most cases, there was massive sepsis leading to the conclusion that primary closure was not advisable. Indicative of the seriousness of these conditions, Apache score averaged 19 (range 10-30). The technique consisted of suturing a double thickness of irrigation bags to each side of the wound, and joining the two bags in the midline with running sutures. Abdominal lavage with large quantities of fluid was performed every other day. This type of closure was used for a mean duration of 15 days. Mean length of hospitalization was 60 days. There were only three deaths (17.6%). No incisional hernia occurred after the iterative laparotomies. Deleting patients with acute pancreatitis would have reduced the death rate to only 7%. A 3L urological irrigation bag costs pound 11.60 (24.40 dollars CAN) while a Marlex mesh costs pound 81.40 (171.00 dollars CAN). We conclude that the usage of 3L urological plastic bags is a simple, safe and efficient method for temporary closure of the abdomen.

Journal Article↗

Lack of skin fibrosis in tight skin (TSK) mice with targeted mutation in the interleukin-4R alpha and transforming growth factor-beta genes.

Scleroderma is a disorder characterized by fibrosis of the skin and internal organs and autoimmunity. Whereas the cause is unknown, interleukin-4 and transforming growth factor-beta have been postulated to play a major part in the fibrosis. To investigate the part played by these cytokines, we prepared TSK/+ mice with a targeted mutation in the interleukin-4R alpha or transforming growth factor-beta genes. The breeding failed to produce TSK/+ transforming growth factor-beta -/- mice so analysis of the role of transforming growth factor-beta was limited to TSK/+ transforming growth factor-beta +/- mice. We observed that TSK/+ interleukin-4R alpha -/- did not develop dermal thickening, and deletion of one allele of the transforming growth factor-beta gene resulted in diminished dermal thickness compared with TSK/+ mice; however, the deletion of interleukin-4R alpha or transforming growth factor-beta had no effect on lung emphysema, which is another characteristic of TSK syndrome. Electron microscopic analysis of skin showed that the collagen fibrils in TSK/+ interleukin-4R alpha -/- mice exhibit normal periodicity but have a smaller diameter than the fibers found in C57BL/6 mice. Analysis of skin and serum samples showed that the deletion of interleukin-4R alpha or one allele of transforming growth factor-beta prevented the increase of skin thickness paralleled with a decrease in the dermal hydroxyproline content and development of autoantibodies associated with TSK syndrome. These results demonstrate the importance of interleukin-4 and transforming growth factor-beta for the development of cutaneous fibrosis in vivo and suggest an important part for these cytokines in wound healing and connective tissue maintenance in general.

Animals↗

Development status of Terumo implantable left ventricular assist system.

We have been developing an implantable left ventricular assist system (T-ILVAS) featuring a magnetically suspended centrifugal pump (MSCP) since 1995. In vitro and in vivo studies using a prototype MSCP composed of a polycarbonate housing and impeller (196 ml) have demonstrated long-term durability and excellent blood compatibility for up to 864 days, and excellent stability of the magnetic bearing of the MSCP. These preliminary results strongly suggested that the magnetic bearing of the MSCP is reliable and is a most feasible mechanism for a long-term circulatory assist device. We have recently devised a clinical version pump made of titanium (180 ml) with a new position sensor mechanism and a wearable controller with batteries. Cadaver fit study confirmed that the Type IV pump could be implanted in a small patient with a body surface area as small as 1.3. The in vitro performance tests of the Type IV pump demonstrated excellent hydrodynamic performances with an acceptable hemolysis rate. New position sensors for the titanium housing showed more uniform sensor outputs of a magnetic bearing than in the prototype polycarbonate pump. The Type IV pump then was evaluated in vivo in 6 sheep at the Oxford Heart Centre. Four sheep were electively sacrificed at 3 months and were allowed to survive for more than 6 months for long-term evaluation. In this particular series of experiments, no anticoagulant/antiplatelet regimen was utilized except for a bolus dose of heparin during surgery. There was a left ventricular mural thrombi around the inflow cannula in 1 sheep. Otherwise, there was no mechanical failure nor sign of thromboembolism throughout the study.

Animals↗

A possible role for maternal HLA antibody in a case of alloimmune neonatal neutropenia.

BACKGROUND: Alloimmune neonatal neutropenia (ANN) is caused by a reaction of maternal alloantibodies with paternally inherited antigens on the fetal neutrophils. While human neutrophil antigens (HNA) antibodies are found in half of ANN cases, specific antibodies have not been defined in the remaining cases. STUDY DESIGN AND METHODS: Reported here is a neonate with omphalitis due to neutropenia. To elucidate the cause of ANN, flow cytometric and PCR analyses were used. Reactions of the patient's and mother's sera with neutrophils, lymphocytes, and platelets were examined by lymphocytotoxicity test (LCT), anti-human immunoglobulin-LCT, and mixed passive hemagglutination test. RESULTS: The maternal sera reacted with neutrophils, lymphocytes, and platelets of the patient and father. The platelet adsorption eliminated the reaction of the maternal serum with the patient's neutrophils. The HLA typing of the family and an LCT using a panel of lymphocytes of 20 HLA-typed donors showed HLA-A2 antigen as a target of antibodies in the maternal serum. According to anti-human immunoglobulin-LCT, the anti-HLA-A2 was present in the neonatal serum. On the other hand, HNA antibodies were not detectable in the patient's or the mother's serum. CONCLUSION: These results suggest that the transplacental passage of the maternal HLA antibody caused neutropenia in this patient.

Adult↗

Antimicrobial activity of new coumarin derivatives.

A preliminary exploration of coumarin analogs as novel antimicrobial agents was carried out to determine the basic features of the structure responsible for the observed biological activity. The substituents ester or carboxylic acid on the coumarin ring were needed to have potent inhibitory activity against both Gram-positive and Gram-negative bacteria. The presence of phenolic hydroxyl group and/or carboxylic acid was necessary to possess higher activity against Helicobacter pylori.

Anti-Bacterial Agents↗

Preclinical evaluation of an immunotherapeutic peptide comprising 7 T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen allergens.

BACKGROUND: Peptide immunotherapy is a new approach to treating allergic diseases, but a therapeutic peptide for Japanese cedar pollinosis has not yet been developed. OBJECTIVE: The aim of this study is to prepare and preclinically evaluate a hybrid peptide comprising 7 T-cell determinants of Cry j 1 and Cry j 2, the major Japanese cedar pollen allergens. METHODS: The recombinant hybrid peptide was prepared after immunodominance of 7 T-cell determinants was confirmed by means of PBMC proliferation assay in 113 volunteers with pollinosis. The hybrid peptide was compared with a mixture of the 7 T-cell determinants in a dose-dependent PBMC proliferation assay in 6 volunteers with pollinosis. PBMC proliferation and binding activity of serum IgE antibody against the hybrid peptide, Cry j 1, and Cry j 2 were investigated in 48 volunteers with pollinosis. RESULTS: The hybrid peptide induced T-cell proliferation with an average 100-fold lower concentration than a mixture of the 7 peptides. PBMCs from 44 (92%) of 48 volunteers proliferated against the hybrid peptide, with significant correlation (r = 0.87) in T-cell proliferation against Cry j 1 and Cry j 2. No serum IgE antibodies specific to Cry j 1 or Cry j 2 bound to the hybrid peptide. CONCLUSION: A hybrid peptide comprising 7 T-cell determinants has the potential for inducing T-cell proliferative responses that is superior to the potential of a mixture of the T-cell determinants and comparable with that of Cry j 1 and Cry j 2. The hybrid peptide will be of use in specific immunotherapy against Japanese cedar pollinosis.

Adult↗