Biomedical subjects

S Iijima

Publications and source records attributed to S Iijima.

At least 19 recordsLinked to original sources

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

The effect of aging on cell-cycle kinetics and X-ray-induced chromosome aberrations in cultured lymphocytes from patients with Down syndrome.

To evaluate the effects of aging on cytogenetic characteristics of lymphocytes from Down syndrome (DS), cell-cycle kinetics after PHA stimulation and chromosome-type aberration frequencies after X-ray exposure were investigated in vitro in the lymphocytes derived from 4 (or 3 for X-ray treatment) age groups of DS patients and age-matched controls. The results clearly showed higher mitotic and proliferation index levels in younger groups compared to older groups at the various culture intervals, whether the lymphocytes were from the DS patients or controls. The age-related changes of the proliferation index were mainly attributed to a delayed response to PHA as age increased. The changes of PHA responses seemed to be particularly marked during adolescence. Nonetheless, no significant differences were observed between the DS patients and age-matched controls for each age group. In all age groups, frequencies of both chromosome-type exchanges and deletions were elevated in the DS patients by about 1.3 times in comparison with the controls. The magnitude of radiosensitivity, however, seemed to decrease slightly in the 40-49-year group. To our knowledge, the present study is the first report in the literature to deal with the effect of aging on the greater radiosensitivity of DS lymphocytes.

Adolescent↗

PubMed1992

Primary systemic amyloidosis: a unique case complaining of diffuse eyelid swelling and conjunctival involvement.

A 52-year-old Japanese woman with the chief complaint of marked swelling of her upper eyelids and a mass over the bulbar conjunctiva is reported. She previously noticed frequent purpura after minimal trauma, which was resolved shortly after taking some ascorbic acid. Laboratory data showed Ig-G kappa type M-protein in the serum and kappa type Bence-Jones protein in the urine by immunoelectrophoresis. Systemic examination showed mild hepatosplenomegaly, 1st degree of AV block, and a mild increase in plasma cells in the bone marrow biopsy. Histologically, the whole dermis of the eyelid skin and conjunctiva was replaced by a large quantity of amorphous, eosinophilic substances, which were diffusely positive with Direct Fast Scarlet 4BS. Immunohistochemical staining was positive for anti-amyloid P component antibody. Typical amyloid fibrils were proved by electron microscopy. She was finally diagnosed as primary systemic amyloidosis with diffuse swollen eyelids and conjunctival mass, symptoms which in primary systemic amyloidosis are very rare.

Amyloidosis↗

PubMed1992

Long-term treatment in infantile choriocarcinoma.

The long-term treatment of a 5 month old boy with precocious puberty secondary to the production of chorionic gonadotropin (hCG) by a choriocarcinoma is described. Of 13 cases of infantile choriocarcinoma reported in the literature, none were successfully treated. The present study describes a partially successful outcome with embolization of a hepatic tumor, irradiation of lung and right submandibular tumors, chemotherapy with methotrexate (MTX), actinomycin D (ACD), cyclophosphamide (CPA) and etoposide (VP16), and splenectomy and hepatic lobectomy. Subsequently, the residual hepatic tumors were treated with high dose melphalan (HDM) followed by reinfusion of unpurged autologous marrow.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Genetic and environmental factors of bone mineral density indicated in Japanese twins.

To evaluate the effects of genetic and environmental factors on the bone mass, we determined the bone mineral density (BMD) in the total body, the lumbar spine and in the femoral neck in 23 Japanese twin pairs including 21 monozygotic (MZ) pairs, applying dual-energy X-ray absorptiometry. In MZ pairs aged 20-49 years, highly significant intraclass correlation coefficients, ranging from 0.775 to 0.926, were observed at several sites, including the lumbar spine and the femoral neck, which suggests considerable contributions of genetic factors to the BMD. Neither intraclass correlation coefficients nor intrapair differences were found to change with increasing age in the present analysis. In female MZ pairs, exercises both at the present time and in the past were correlated with the BMD at several sites as well as body mass index in multiple regression analyses.

Absorptiometry, Photon↗

PubMed1992

[Comprehensive activities of daily living (ADL) index for the elderly].

In order to measure disability in the elderly with a variety of handicaps a comprehensive activities of daily living (ADL) index is described. This instrument, named the ADL-20, consists of 20 items from four major categories of daily activities: (1) 5 items from basic ADL for mobility (BADLm), (2) 6 items from basic ADL for self-care (BADLs), (3) 7 items from instrumental ADL (IADL), and (4) 2 items from communication ADL (CADL). Each activity is scored on a four point scale with values from 0 (total dependency) to 3 (independency). In order to study the interrater reliability of the instrument 40 subjects were examined by a physician and physiotherapist independently at the University of Tokyo Hospital on the same day. Perfect agreement rates on the assignment of the disability score ranged from 70.0% to 97.5% with 85.6% in 800 paired examinations. The kappa values for perfect agreement ranged from 0.52 to 0.88. These results may guarantee a moderate or greater degree of interrater reliability. The correlation coefficients of the Spearman test on the rating scores by the physician and physiotherapist ranged from 0.66 to 0.99 in each activity with 0.97 in total score of 20 items. This scale was employed in 110 patients at the University Hospital and 106 patients staying in the nursing home or long-stay geriatric hospital in order to study its validity. The average age of those 216 patients, 77 males and 139 females, was 76.2 years old. The Cronbach alpha value concerning the consistency of each item as ADL assessment scale was 0.97.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗

PubMed1992

Stabilities of antigen and antibody under elution conditions in immunoaffinity chromatography using monoclonal antibody.

In immunoaffinity chromatography using monoclonal antibody, the elution conditions of an antigen, recombinant alpha-amylase, were studied. From among various conditions, three elution methods that gave fairly good yields of antigen activity (pH 2.3-2.5, pH 12.3-12.5 and 0.1 M lithium 3,5-diiodo salicylate [LIS]) were selected and the stabilities of the antigen and the antibody were analyzed. The antigen seemed to be eluted from the immunoadsorbent due to partial denaturation of either the antigen or the antibody. LIS seemed to be a specific denaturant for the antibody and its action was reversible. In terms of the stability of the antigen and repeated use of the immunoadsorbent, LIS seemed to be the best reagent for elution in immunoaffinity chromatography.

Animals↗

PubMed1992

Analysis for cerebrospinal fluid proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Cerebrospinal fluid (CSF) proteins with molecular masses of < 150,000 Da were identified by immunoblotting after two kinds of nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). With PAGE 1 (17-27% gradient gel), CSF proteins were clearly separated into seven to nine bands with molecular masses of 3000-67,000 Da; seven bands were identified as beta 2-microglobulin, lysozyme, prealbumin, free kappa and lambda chain, apolipoprotein A-I, glycoproteins, and albumin by immunoblotting. With PAGE 2 (10-20% gradient gel), proteins were clearly separated into 11-16 bands with molecular masses of 15,000-150,000 Da; 11 were identified as prealbumin, free kappa and lambda chain, apolipoprotein A-I, glycoproteins, albumin, alpha 1-antitrypsin, transferrin (separated into two bands), immunoglobulin fragments, haptoglobin, and IgG. We analyzed CSF samples collected from 81 patients with cerebrospinal signs by these SDS-PAGE methods and observed prominent bands in some cases.

Adolescent↗

PubMed1992

[A study on a postoperative change of beta-2-microglobulin in surgical patients].

Various renal tubular functions were monitored perioperatively in 42 surgical patients and the validity of beta-2-microglobulin (BMG) was evaluated. NAG index (urine NAG titer/urine creatinine), the absolute value of free water clearance and fractional excretion of sodium were worse at 3 to 5 hours after the beginning of operation, indicating the latent renal tubular damage took place during operation. On the other hand, fractional excretion of BMG (FE-BMG; BMG clearance/creatinine clearance) slowly elevated after operation and reached a peak on the 2nd postoperative day. The postoperative change of C-reactive protein (CRP), was similar with that of FE-BMG, showing a significant correlation (r = 0.716, p less than 0.001). The close relationship between CRP and FE BMG was confirmed in 26 patients with or without abnormal liver function who underwent abdominal operation. The peak value of FE BMG was significantly (p less than 0.01) lower in 5 patients with ICG 15' greater than 25% than in 21 patients with ICG 15' less than 20%. Similarly, the peak value of CRP tended to be lower in the former group. In conclusion, FE BMG can not be employed as an indicator of renal tubular function during postoperative period. It reacts as an acute phase reactant like CRP and is probably produced in the liver.

Acetylglucosaminidase↗

PubMed1991

Evaluation of the reticuloendothelial system function by the vascular clearance of chondroitin sulfate iron colloid.

Vascular clearance of chondroitin sulfate iron colloid (CSFe) was evaluated as a test for the reticuloendothelial system (RES) in rabbits. Injected CS59Fe was taken up by the RES in the liver (49%) and bone marrow (41%) after 60 min, suggesting its application for the RES function test. The clearance rate (K-value) of CSFe from the blood was calculated by measuring serum Fe concentrations after releasing iron from CSFe at certain intervals after injection. Depending upon different injected doses, K-values were varied and the phagocytic velocity, computed by multiplying K-values by corresponding injected doses, reached a plateau at high doses, indicating the phagocytosis of CSFe by the RES takes a saturation process. Double-reciprocal plotting of the dose and the phagocytic velocity showed a linear relationship, which provided the data on the maximum phagocytic velocity (Vmax), 0.122 mg/kg/min, and the CSFe concentration producing 1/2 Vmax (Kp), 0.426 mg/kg. Thus, this CSFe clearance test can be used for the evaluation of the RES function.

Animals↗

PubMed1991

[Prevention and treatment of dementia: what should we do today?].

Three studies were conducted on elderly patients with dementia. A case of control study on life styles before falling ill revealed that "intake of sweets" was significantly associated with clinically diagnosed dementia of the Alzheimer's type. Evaluation of treatments of outpatients suggests that proper care and some kinds of neuroleptics are useful for alleviation of abnormal behavior such as agitation, wandering, hallucination, insomnia and depression, but not for improvement of cognitive function and memory. A study on caregivers of elderly demented patients was undertaken to determine the relationship between the components of burden and symptoms of patients. Insomnia and abnormal behavior of patients correlated with physical and mental components of the burden of caregivers. Memory disturbance, psychological symptoms and deterioration in ADL correlated with physical burden. These studies indicate that symptoms accompanying dementia such as insomnia, wandering, hallucination and agitation should be the treated intensively for the purpose of improvement of the quality of the lives of patients and caregivers.

Aged↗

PubMed1990

Enhanced phosphorylation of a nucleolar 110-kDa protein in rat liver by dietary manipulation.

RNA polymerase 1 activity and nucleolar volume have been reported to increase in hepatocytes from rats fed a protein-free diet. Phosphorylation in vitro of a 110-kDa protein was enhanced in nuclei and nucleoli from livers of rats fed a protein-free diet. In nuclear extracts the 110-kDa protein in heat-treated nuclei was much more phosphorylated than from control liver. In contrast, casein kinase activity in the nuclear extract from control liver was comparable to that from livers of rats fed a protein-free diet. Nuclear extracts from control rat liver and livers of rats fed a protein-free diet were fractionated by DEAE-cellulose column chromatography. Casein kinase II (NII) eluted at around 0.17 M NaCl scarcely phosphorylates the 110-kDa protein. Chromatography of the nuclear extract from livers of rats fed a protein-free diet, but not from control liver, yielded fractions which eluted at 0.21-0.25 M NaCl and predominantly phosphorylated the 110-kDa protein. The phosphorylation of 110-kDa protein was not appreciably affected by a heparin concentration of 5 micrograms/ml, which completely inhibited casein kinase II. In addition, phosphorylation of the 110-kDa protein in liver nucleoli from rats fed a protein-free diet showed a lower sensitivity to heparin than that in control rat liver nucleoli. These results suggest that enhanced phosphorylation of the nuclear 110-kDa protein in livers from rats fed a protein-free diet is due to the induction of a 110-kDa protein kinase distinct from casein kinase II.

Adenosine Triphosphate↗

PubMed1990

Comparison of oxygen supply methods for cultures of shear-stress sensitive organisms including animal cell culture.

In animal cell culture, oxygen supply sometimes limits cell growth. Therefore, four oxygen supply methods (free surface aeration, porous Teflon tubing, perfluorocarbon addition and external aerator) were compared in terms of oxygen transfer rate for suspension culture of animal cells. Oxygen transfer rate with the free surface aeration was dependent on the vertical position of the impeller and the stirred Reynolds number for h/HL greater than 0.35, but no effect of the impeller position was observed for h/HL less than 0.35. The relationship between the Reynolds and Sherwood numbers could be expressed by simple correlations. These correlations could also be applied to oxygen transfer using porous Teflon tubing. When oxygen was supplied with perfluorocarbon saturated with air, the overall mass transfer coefficient KL was estimated to be about 9.0 X 10(-3) cm s-1, which was five-fold greater than that of the surface aeration. Maximum cell densities which would be supported by four methods were calculated from values of KLa for different sizes of fermentor assuming that oxygen supply would be the rate-limiting factor in animal cell culture.

Animals↗