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Biomedical subjects

S Iijima

Publications and source records attributed to S Iijima.

At least 127 records · Page 7Linked to original sources

The carbohydrate moiety of the acid carboxypeptidase from Aspergillus saitoi.

Acid carboxypeptidase from Aspergillus saitoi is a glycoprotein that contains both N- and O-linked sugar chains. The N-glycanase released high-mannose type oligosaccharides that were separated into eight components on HPLC. One, which had a unique structure of Man11GlcNAc2, was characterized. Mild alkali treatment of the carboxypeptidase, under conditions that effect beta-elimination, yielded D-mannose. Deglycosylation of the carboxypeptidase with endo-beta-N-acetylglucosaminidase and alpha-mannosidase effected the reduction of the molecular mass from 72 kDa to 60 kDa. Partial changes of CD spectra of the native and the deglycosylated enzymes indicate that some conformational changes on the peptide of the enzyme occurred after deglycosylation. Other enzymatic properties, such as catalytic activity, pH, and thermal stability and resistivity to protease digestion, did not appear to change. Tunicamycin halted secretion of the carboxypeptidase extracellularly.

Aspergillus↗

Phenserine: a physostigmine derivative that is a long-acting inhibitor of cholinesterase and demonstrates a wide dose range for attenuating a scopolamine-induced learning impairment of rats in a 14-unit T-maze.

Phenserine ((-)-N-phenylcarbamoyl eseroline), a carbamate analog of physostigmine (Phy), is a long-acting inhibitor of cholinesterase. We have assessed the potential clinical value of phenserine for cholinomimetic therapy of cognitive impairments associated with aging and Alzheimer's disease by evaluating its duration of in vivo activity against rat plasma acetylcholinesterase (AChE) and its effect on attenuating a scopolamine-induced impairment in learning performance of young rats in a shock-motivated 14-unit T-maze. Phenserine achieved maximum AChE inhibition of 73.5% at 5 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, 69, 3-month-old male Fischer-344 rats were pretrained in a straight runway to avoid electric footshock. On the following day, each animal received 15 trials in the 14-unit T-maze. Sixty minutes prior to the maze training, each rat received the first IP injection of either vehicle (Tween 80, ethanol and 0.9% NaCl) or phenserine at 1.5, 3.0, 4.0, 5.0, 7.5, or 10.0 mg/kg. Then 30 min prior to the training, each animal received a second IP injection of either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg; SCOP). Compared to the vehicle-SCOP group, all but the 7.5 mg/kg dose of phenserine significantly ameliorated error performance, runtime, shock frequency and shock duration in SCOP-treated rats at the final block of three trials. Appearing to have a long effect and a wide therapeutic window, phenserine deserves further study as a cognitive enhancer.

Acetylcholinesterase↗

Effect of acupuncture at the right Hoku point on bilateral vibration-induced finger flexion reflex in man: comparison between in-situ and Sparrow Pecking technique.

The purpose of this study was to compare the effect of the Sparrow Pecking (SP) technique with that of the In-Situ (IS) technique of acupuncture on vibration-induced finger flexion reflex (VFR). Subjects were 30 healthy adults. VFR, flexion movement of the vibrated finger, was induced by vibrating the volar side of the middle finger tip. The acupuncture point was the right Hoku point. Both techniques of acupuncture inhibited VFR in the ipsilateral and contralateral sides, but inhibition with SP was significantly greater than that with IS (percentage control force of VFR, mean +/- SD: with SP right, 62.1 +/- 24.6%, left, 60.6 +/- 27.9%, with IS right, 74.9 +/- 26.6%, left, 78.1 +/- 29.5%, P < 0.0005). The results suggest that SP suppresses facilitation of VFR in the reflex arcs more than IS does.

Acupuncture Points↗

Effect of platelet on protein degradation in rat skeletal muscle.

The effects of activated platelet (Plt) on muscle degradation were investigated, employing the in vivo disseminated intravascular coagulation (DIC) model induced by thrombin injection and the in vitro tissue culture system of skeletal muscles in rats. Both the release of tyrosine and leucine into the culture medium during 2 h incubation from the muscles harvested 30 min after thrombin injection increased by about 50% compared with control muscles. The addition of thrombin-activated platelet supernatant (TAPS) significantly increased the release of leucine into the incubation medium of the soleus muscles dissected from normally fed rats by 31% in comparison with the respective controls. No significant effect was observed in terms of the release of tyrosine or leucine from the incubated muscles by aspirin treatment before obtaining TAPS, or by the addition of thrombin itself up to the concentration of 0.67 micron/ml which was contained in the incubation medium of TAPS. These data suggest that protein catabolism is accelerated in the muscle from the thrombin-treated rats exhibiting DIC. The supernatant of activated Plt might contain a factor which modulates protein metabolism. That factor is different from prostaglandins or thrombin. Thus, active consumption of Plt may contribute to an increase of muscle breakdown in various catabolic states.

Animals↗

Contact immunotherapy with squaric acid dibutylester for warts [corrected].

The efficacy of squaric acid dibutylester (SADBE), a topical allergen, was investigated in the treatment of 20 patients with warts. All patients had multiple or warts recalcitrant to other therapies or hesitated to have the painful cryotherapy. The patients with warts present for a mean of 15.3 months (range 1-36) were successfully sensitized with 2% SADBE in acetone. Then the warts were treated with a 0.1 or 0.01% SADBE application once a week or every other week, so as to maintain a mild contact dermatitis. Twelve of the 20 patients (60%) were completely cured after an average of 6 applications (range 2-12). Five patients (25%) showed either a poor or no response even after 9-18 applications. Three patients (15%) exhibited contact dermatitis either at the sensitization or the treatment site. Our study shows that this therapy, although not always safe, is effective in treating warts in some patients, who either hesitate at conventional cryotherapy or have warts resistant to other therapies. The safety of this method remains to be evaluated.

Administration, Cutaneous↗

Central neural mechanism contributing to attenuation of angiotensin II-induced hypertension in rats on dietary calcium supplementation.

The effect of dietary calcium (Ca) supplementation on blood pressure (BP) and the central nervous system (CNS) mechanism underlying this effect were studied in angiotensin II (Ang II)-induced hypertensive rats. The effects of dietary Ca (0.5, 2, 4%) on systolic blood pressure (SBP), ionized Ca concentration (Ca++) in cerebrospinal fluid (CSF) and central norepinephrine (NE) turnover were investigated in male Wistar rats receiving subcutaneous infusion of Ang II (100 ng/min). Central NE turnover was studied by measuring 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration in CSF with multiple electrode liquid chromatography. Ang II significantly increased SBP, and dietary Ca dose-dependently attenuated the increase. SBP inversely correlated with Ca++ and MHPG in CSF. Intracerebroventricular injection of CaCl2 more markedly reduced BP in Ang II-treated rats than that in control rats. These results suggest that modulation of central NE turnover possibly caused by the increase in CNS Ca++ is involved in the anti-hypertensive mechanism of dietary Ca supplementation in Ang II-induced hypertensive rats.

Angiotensin II↗

[Concentrations of multiple neurochemicals in the cerebrospinal fluid of patients with senile dementia and the relationship to alpha 1-antichymotrypsin].

The authors investigated the concentrations of multiple neurochemicals (6 kinds of catecholaminergic and 5 kinds of indolaminergic substances) in the lumbar cerebrospinal fluid (CSF) of patients with and without senile dementia (13 Alzheimer type (AD), 7 vascular type (VD), 11 Parkinson's disease (PD) and 9 non-demented controls (C)) by means of a neurochemical analyzing system (Neurochem, ESA). By means of the enzyme-linked immunosorbent assay (ELISA), we also determined the concentration of alpha 1-antichymotrypsin (ACT) in the CSF, which may be a possible diagnostic biochemical marker of the senile dementia of Alzheimer type. ACT in CSF was significantly higher in the AD group. It correlated negatively with Hasegawa's dementia scale (HDS) significantly. It also correlated negatively with the concentration of HVA significantly and showed tendency to correlate with the concentrations of dopamine and the ratio of kynurenine and tryptophan (KYN/TRP). Each dementia group showed characteristic concentration patterns of neurochemicals (DA, HVA, MHPG/NE, KYN/TRP, and 5-HIAA/5-HT). Our approach may provide a new quantitative method to diagnose geriatric neuropsychological diseases as well as senile dementia.

Aged↗

[Reliability and validity of a Japanese version of the Dementia Behavior Disturbance Scale].

Since behavioral disturbance among patients with dementia is a great burden for their caregivers, quantification of behavioral disturbance is essential in determining disease severity and assessing the impact of the disease on caregivers. However, the method of its quantification for objective assessment is not established yet. We studied the reliability and validity of a Japanese version of the Dementia Behavior Disturbance Scale (DBD Scale) which was originally developed by Baumgarten et al. We also studied the relationship between DBD scores and the degree of burden felt by caregivers. Our subjects consisted of 27 cases with dementia (mean age 77.7 years), and 17 cases of patients with neurological disorders without dementia (76.8 years), and 10 institutionalized patients with dementia (82.3 years). The test-retest reliability, internal consistency, and inter-rater reliability were very good; the coefficient of correlation between DBD scores at the two interviews was 0.96, the coefficient of internal consistency was 0.95, and the intraclass correlation coefficient was 0.71 +/- 0.10. DBD scores correlated significantly with SPMSQ errors and caregivers' burden; r = 0.54 and 0.53, respectively. Our results indicate that the DBD Scale is highly reliable, and may be useful for objective assessment of behavioral disturbance and caregivers' burden.

Aged↗

[Leukocyte activity and occurrence of tissue injury by G-CSF].

G-CSF (granulocyte-colony stimulating factor) is one of the cytokines which increase and activate neutrophils. These effects have been confirmed by a lot of clinical studies. Although only few side effects have been reported so far, we saw a patient with hypertension, facial edema, and severe headache after G-CSF administration. We have measured the sticking strength of leukocytes to the walls of narrow pores in modified Nuclepore filtration method of Kikuchi, in various clinical situations, and we have denoted the pore filtration time as the rheological activity of leukocytes (RAL). In this study, we tried to measure RALs of patients after G-CSF administration (60-100 micrograms) and to compare them with those of non-treated normal individuals. We also checked serum levels of granulocyte elastase in the patients. In the static state (in which neutrophils were not stimulated), RALs of the patients were 8.0 +/- 1.5sec. [N = 8], and those of the controls were 3.8 +/- 1.6sec. [N = 21] (p < 0.001). In the activated state (in which neutrophils were stimulated by formyl-methionyl-leucyl-phenylalanine), PALs of patients were quite high, i.e. those of the patients and controls were 592 +/- 322sec. and 69 +/- 62sec., respectively (p < 0.001). In all cases given G-CSF, the serum levels of granulocyte elastase were above the normal range. In view of our results, we it is possible that highly activated leukocytes would injure tissue and then induce organ failure and several symptoms, as in this study.

Adult↗

Schedule-dependent inhibition of thymidylate synthase by 5-fluorouracil in gastric cancer.

BACKGROUND: An optimal treatment schedule of 5-fluorouracil (5-FU) remains to be clarified. METHODS: A randomized study was conducted to investigate schedule-dependent thymidylate synthase (TS) inhibition by 5-FU in 16 patients with gastric cancer who underwent surgical resection. Surgical specimens of tumor, normal gastric mucosa, and regional lymph nodes were obtained 12 hours after administration of 5-FU either as a continuous infusion (1000 mg/m2 for 48 hours) or as a bolus injection (500 mg/m2 x 2 in 48 hours). RESULTS: The total TS activity (567.8 +/- 294 fmol/mg protein) and the rate of TS inhibition (74.7 +/- 23.1%) in cancer tissues were significantly higher in the continuous-infusion group than in the bolus-injection group (228.5 +/- 104.6 fmol/mg protein and 48.8 +/- 12%, respectively). Likewise, the total TS activity (807.4 +/- 440.3 fmol/mg protein) and the rates of TS inhibition in lymph nodes (72.3 +/- 17.1%) and in normal gastric mucosa (85.1 +/- 12.2%) were significantly higher in the continuous-infusion group than those in the bolus-injection group (232.4 +/- 142.3 fmol/mg protein and 53.6 +/- 17.0% in lymph nodes and 46.5 +/- 14.3% in normal gastric mucosa, respectively). There was a significant correlation between the total TS activity and TS inhibition. CONCLUSIONS: Continuous infusion of 5-FU provides a superior antimetabolic effect in the treatment of gastric cancer, which may lead to a superior antitumor effect.

Aged↗

The long-acting cholinesterase inhibitor heptyl-physostigmine attenuates the scopolamine-induced learning impairment of rats in a 14-unit T-maze.

Heptyl-physostigmine (heptyl-Phy), a new carbamate derivative of physostigmine (Phy), has been assessed for potential clinical value by evaluating its in vitro activity against human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE), its duration of in vivo activity against rat plasma AChE, and its effects on attenuating a scopolamine-induced impairment in learning performance of young rats in a 14-unit T-maze. Heptyl-Phy demonstrated potent cholinesterase inhibition, with activity similar to that of Phy against AChE, IC50 values 21.7 +/- 2.0 nM and 27.9 +/- 2.4 nM, respectively, and significantly greater than that of Phy against BChE, IC50 values 5.0 +/- 0.1 nM and 16.0 +/- 2.9 nM, respectively. Heptyl-Phy achieved maximum AChE inhibition of 92.5% at 60 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, heptyl-Phy at 1.0, 1.5, 2.0 or 3.0 mg/kg, or vehicle was administered i.p. to 52 3-month-old male Fischer-344 rats 60 min prior to maze training. Thirty minutes prior to training, each animal received either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg). Only a 2.0 mg/kg dose of heptyl-Phy significantly reduced the number of errors in scopolamine-treated rats. The other doses did not improve any aspect of maze performance. Although the therapeutic window of heptyl-Phy did not appear wide enough for clinical use, the longer duration of action of heptyl-Phy would appear beneficial.

Acetylcholinesterase↗

DNA-activated protein kinase in Raji Burkitt's lymphoma cells. Phosphorylation of c-Myc oncoprotein.

Autophosphorylation of a DNA-activated protein kinase (DNA-PK) in Raji Burkitt's lymphoma cells generated a band that corresponded to a phosphoprotein of about 300 kDa on SDS/PAGE. This band corresponds to a 300-350-kDa DNA-PK found previously in HeLa cells. In addition to the 300-kDa phosphoprotein, the band of a highly phosphorylated 58-kDa protein was detected by SDS/PAGE of partially purified DNA-PK preparations after the phosphorylation reaction in the presence of double-stranded DNA. This phosphoprotein was specifically immunoprecipitated by phosphoprotein nor detectable activities of other kinases, phosphorylated recombinant c-Myc proteins in the presence of DNA. The c-Myc phosphorylation by DNA-PK was markedly stimulated by relaxed, double-stranded DNA, but neither by single-stranded DNA nor by RNA. Phosphopeptide mapping and phosphoamino acid analysis indicated that DNA-PK phosphorylates c-Myc in vitro at several serine residues.

Amino Acid Sequence↗

Possible Werner syndrome. A unique association with spontaneous digital gangrene in infancy and decreased life span of cultured skin fibroblasts.

BACKGROUND: Werner syndrome is a hereditary disease characterized by several features generally associated with aging. However, the differences between Werner syndrome and the normal aging process are clear. Werner syndrome is usually diagnosed through the clinical signs and symptoms it presents. In recent years, however, the cultured skin fibroblasts of patients have grown slowly and patients have a short life span; these characteristics provide a useful diagnostic aid. OBSERVATIONS: We recently examined a 42-year-old single man who had short fingers, marked facial scars resulting from chilblain-like eruption in infancy, glaucoma caused by uveitis developed in his middle age, callosities on the soles, and immaturation of sexual glands. Repeated peripheral blood examinations showed a positive result for antinuclear factor, slight elevation of immunoglobulin levels, and a low leukocyte count. His family had repeated consanguineous marriages and his parents were cousins. We cultured skin fibroblasts from the patient's forearm and compared them with those of four normal control male subjects. The patient's skin fibroblasts showed a remarkably low population growth rate and a total replicative life span. CONCLUSION: The patients presented unique clinical features for Werner syndrome such as chilblain-like eruption in infancy and glaucoma caused by uveitis. Cell culture studies revealed cellular abnormalities compatible with Werner syndrome. We thus diagnosed the patients as possibly having Werner syndrome.

Adult↗

Increased soluble CD4 and decreased soluble CD8 molecules in patients with Sjögren's syndrome.

PURPOSE: A new enzyme-linked immunosorbent assay for soluble CD4 (sCD4) and soluble CD8 (sCD8) molecules has been developed. We estimated the concentrations of these molecules in patients with Sjögren's syndrome and in patients with systemic lupus erythematosus (SLE) serving as a control population for non-Sjögren's inflammatory disease, since several findings suggestive of an aberration of immunocompetent cells have been reported in these autoimmune diseases. PATIENTS AND METHODS: The study population consisted of 41 patients with Sjögren's syndrome (28 cases of the primary form and 13 cases of the secondary form), 66 patients with SLE, and 43 normal individuals. Serum samples and clinical and laboratory data were collected from each patient and control. Assays of the sCD4 and sCD8 molecules were performed using an enzyme-linked immunosorbent kit developed by T Cell Science Inc., Cambridge, MA. RESULTS: The concentration of sCD4 was significantly increased in patients with both primary and secondary Sjögren's syndrome as compared with that in the control subjects. In contrast, sCD8 was significantly decreased in patients with primary disease but not in patients with secondary disease. A low or high concentration of sCD8 was significantly correlated with the presence of anti-SS-A antibody or hypocomplementemia, respectively. A similar significant correlation was noted between an increased sCD4 concentration and increased serum IgG level. In patients with SLE, the levels of both sCD4 and sCD8 were significantly increased. CONCLUSION: These observations represent the first evidence of an increased level of the sCD4 molecule and a decreased level of the sCD8 molecule and an association with immunologic abnormalities in Sjögren's syndrome. The increased and decreased levels of these soluble molecules observed may play a pathologic role in patients with Sjögren's syndrome.

Adult↗

Establishment of a multi-dose study of chondroitin sulfate iron colloid for evaluation of the reticuloendothelial system function.

The assay system of chondroitin sulfate iron colloid (CSFe) was established to evaluate the reticuloendothelial system (RES) function in individual rabbits. In the multi-dose study of CSFe, CSFe was repeatedly administered to each individual rabbit with increasing doses (0.6, 1.2, 2.4, 6.0 mg/kg) at set intervals. Blood samples were serially collected after injection of CSFe and the concentration of CSFe in serum was directly measured as an iron concentration by modifying the previously described assay method [1] to minimize the sample volume. The clearance rate of CSFe at each injected dose was computed by the least-squares method and the double-reciprocal plotting of the doses against the phagocytic velocities by the Lineweaver-Burk method was obtained in each rabbit. The maximum phagocytic velocity (Vmax) and the CSFe concentration producing 1/2 Vmax (Kp) obtained in ten rabbits were 0.129 +/- 0.025 mg/kg per min and 0.417 +/- 0.121 mg/kg (mean +/- S.D.), respectively. The results obtained from this multi-dose study were comparable to our previous results obtained from the mean values of five groups given different doses [1]. The clearance rates of CSFe (0.6, 1.2, 6 mg/kg) decreased after the co-injection of 80 mg/kg of carbon colloid. The calculated Vmax and Kp in 29 rabbits were 0.125 mg/kg per min and 1.167 mg/kg. The Kp was apparently greater than that of the control (Vmax = 0.128 mg/kg per min, Kp = 0.421 mg/kg). Carbon colloid (80 mg/kg) was injected to six rabbits after the completion of the first multi-dose study of CSFe and then the second multi-dose study of CSFe was repeated after 24 h. No differences were found in Vmax and Kp between the two studies as were in the control group (10 rabbits) where saline was injected instead of carbon colloid. These results indicated that carbon colloid (80 mg/kg) gives a competitive and reversible inhibition on the RES. This multi-dose study of CSFe may be applicable for a bed-side analysis of the RES function in a patient.

Animals↗