[A new anti-cancer agent K-18 (conjugate of human IgG and melphalan). (II). Its inhibitory effects on in vitro DNA synthesis of human tumor cells].
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Antineoplastic Agents↗
Biomedical subjects
S Imai
Publications and source records attributed to S Imai.
[A new anti-cancer agent K-18 (conjugate of human IgG and melphalan). (I). K-18 accumulates selectively into the tumor].
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Administration, Oral↗
Production of human monoclonal antibodies against Epstein-Barr virus-specific antigens by the virus-immortalized lymphoblastoid cell lines.
The possible production of human monoclonal antibodies against Epstein-Barr virus (EBV) was assessed through the EBV immortalization technique. When individual lymphocyte samples from 50 clinical patients and healthy donors were immortalized by EBV, 4 lymphoblastoid lines yielded antibodies to EBV antigens. These positive lines were cloned and each line yielded cultures that secreted monoclonal antibodies against either viral capsid antigen (VCA) or membrane antigen (MA) component. Above all, a clonal line TAKA-SP-8 produced 5 micrograms MA antibody/10(6) cells/ml for more than 12 months. The culture fluid specifically immunoprecipitated a single polypeptide with a size of 93K from both P3HR-1 and B95-8 cell extracts. FUKA-SP-3, on the other hand, secreted 5 micrograms VCA antibody/10(6) cells/ml for at least 8 months. This antibody recognized two polypeptides with sizes of 123K and 120K, from P3HR-1 and B95-8 cell extracts, respectively. When B95-8 and P3HR-1 EBV were treated with the human MA monoclonal, both nuclear antigen (EBNA) synthesis and early antigen (EA) induction were strongly inhibited. All EBV antibody-producing cultures were exclusively achieved from splenic lymphocytes of patients with autoimmune diseases, but not from other donors.
Antibodies, Monoclonal↗
Difference in mode of inhibition between alpha-D-xylosyl beta-D-fructoside and alpha-isomaltosyl beta-D-fructoside in synthesis of glucan by Streptococcus mutans D-glucosyltransferase.
Both alpha-isomaltosyl beta-D-fructoside and alpha-D-xylosyl beta-D-fructoside show strong inhibition of the synthesis of water-insoluble and water-soluble D-glucans from sucrose by a partially purified preparation of a D-glucosyltransferase (GTase) from Streptococcus mutans 6715; however, the inhibitory modes differ substantially. In the presence of alpha-isomaltosyl beta-D-fructoside, the production of reducing sugars and the consumption of sucrose are remarkably enhanced, compared with a control of sucrose alone. Under these conditions, a large proportion of low-molecular-weight glycan (lmwg) and a series of nonreducing oligosaccharides (both containing D-fructosyl groups or residues) are produced. In contrast, in the presence of alpha-D-xylosyl beta-D-fructoside, the production of reducing sugars and the sucrose consumption are strikingly suppressed, and no lmwg or oligosaccharides are produced. Thus, it may be concluded that alpha-isomaltosyl beta-D-fructoside acts as an alternative acceptor for the D-glucosyl and/or D-glucanosyl transfer reactions of the enzyme, and serves to lessen the formation of insoluble and soluble D-glucan, although it stimulates the transferring activity of the enzyme. On the other hand, alpha-D-xylosyl beta-D-fructoside competitively inhibits the sucrose-splitting activity of the enzyme as an analog to sucrose, and thereby diminishes the synthesis of D-glucan.
Disaccharides↗
Pentylenetetrazole-induced bursting activity and cellular protein phosphorylation in snail neurons.
To elucidate the intracellular mechanism of seizure discharge, phosphorylation of cellular protein during pentylenetetrazole (PTZ)-induced bursting activity in snail neurons was investigated. PTZ markedly enhanced the phosphorylation of proteins of 34,000 and 50,000 molecular weight. Similar effects were observed by application of a calcium ionophore, A23187. Calmodulin antagonist, N-(6-aminohexyl)-5-chloronaphthalenesulfonamide hydrochloride (W-7), inhibited the PTZ-induced increased phosphorylation of these two proteins. Dibutyryl cyclic AMP and iosobutylmethylxanthine (IBMX) showed no significant effect on the phosphorylation pattern. Bath application of the calcium ionophore produced bursting activity followed by long-lasting hyperpolarization. Bath application of W-7 completely inhibited the PTZ-induced bursting activity. These results suggest that the phosphorylation of proteins of 34,000 and 50,000 in molecular weight is related to the generation of bursting activity by PTZ.
Animals↗
Trace elements in human hair: an international comparison.
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Adolescent↗
Stimulation of synapsin I phosphorylation in synaptosomes by convulsants.
Pentylenetetrazole markedly enhanced synapsin I (previously referred to as protein I) phosphorylation and synaptosomal uptake of Ca2+. Picrotoxin and strychnine sulfate caused a slight increase in the phosphorylation and no significant increase in Ca2+ uptake. The data indicate that pentylenetetrazole appears to influence this process.
Animals↗
Membrane properties and intracellular biochemical processes during vasopressin-induced bursting activity in snail neurons.
To elucidate the mechanism generating bursting activity, the effect of arginine vasopressin (AVP) was studied electrophysiologically and biochemically in ganglionic preparations from the snail, Euhadra peliomphala. AVP caused bursting activity which is accompanied by the development of a negative slope resistance (NSR) region in the current-voltage (I-V) curve of the identified neurons. Similar effects were observed by application of veratridine, dibutyryl cyclic AMP and isobutylmethylxanthine. Both the bursting activity and the I-V relation induced by AVP were markedly inhibited by reduction of extracellular Na+ but not by Co2+-substituted Ca2+-free saline. This hormone also caused the following intracellular biochemical alterations: elevation in the cyclic AMP levels; stimulation of adenylate cyclase and Ca2+-dependent protein kinase activities; and promotion of Ca2+ release from the intracellular reservoir, lysosome-like granules. These results suggest that AVP-induced bursting activity is mediated through intracellular biochemical processes.
Adenylyl Cyclases↗
Thymosin alpha 1 enhances haemopoietic colony formation by stimulating the production of interleukin 3 in nu/nu mice.
We have studied the action mechanism of thymosin alpha 1 in modulation of haemopoietic system. The present study demonstrated that thymosin alpha 1 enhanced the colony formation as determined by CFU-s, GM-CFU and T-CFU, as well as the production of IL-3, when administered twice a week for a total of six or twelve times into nu/nu mice. The incubation of bone marrow cells with thymosin alpha 1 in vitro did not cause an increase of CFU-s, in contrast to IL-3 which caused a marked increase of CFU-s during the incubation of 72 h. These experiments indicate that thymosin alpha 1 exerts its effect on colony formation of haemopoietic stem cells (CFU-s) indirectly through the enhancement of the IL-3 production. The present finding may support clinical applications of thymosin alpha 1 in a wide range, since IL-3 is known to be the growth factor for many kinds of haemopoietic precursor cells including not only CFU-s but also GM-CFU, BFU-E, Eos-CFU, Meg-CFU, Mast cells, Pre B-cells and Pre T-cells.
Animals↗
Role played by oxygen in myocardial protection with crystalloid cardioplegic solution.
To evaluate the importance of the oxygen dissolved in crystalloid cardioplegic solution, the protective effects of oxygenated glucose-insulin-potassium cardioplegic solution (O2-GIK) (oxygen tension greater than 600 mm Hg) on the isolated working guinea pig heart were compared with those of deoxygenated (N2-GIK) (oxygen tension less than 10 mm Hg) and aerated GIK solution (GIK) (oxygen tension = 140 to 160 mm Hg). Hearts were subjected to 180 minutes of ischemia with intermittent infusions (every 30 minutes) of cold cardioplegic solution, followed by 30 minutes of normothermic reperfusion. The O2-GIK solution tended to maintain high-energy phosphates at higher levels during ischemia, and resulted in the best recovery of cardiac function. Though not as effective as O2-GIK, GIK solution produced protective effects; N2-GIK solution failed to exert such effects. These results strongly suggest that the protective effects of crystalloid cardioplegic solution are due primarily to the oxygen dissolved in it; anaerobic metabolism or washout of the metabolites plays a minor part.
Animals↗
Visual training and correction of articulation disorders by use of dynamic palatography: serial observation in a case of cleft palate.
The dynamic palatograph is an electrical apparatus that generates a visual display of constantly changing palatolingual contact as a function of time, using an artificial palatal plate with affixed electrodes. This paper describes a technique of speech therapy incorporating dynamic palatography for a cleft palate patient. The patient, a 6-year-old Japanese girl with a repaired unilateral cleft lip and palate, had been judged to demonstrate articulation disorders involving contact of the tongue with the hard palate or alveolus following surgical improvement of velopharyngeal function. Prior to therapy the tongue tended to contact the hard palate more posteriorly than normal. After therapy with the dynamic palatograph, palatolingual contact was normal in comparison with average speakers. Our findings suggest that the facility of constant visual indication of tongue posture to the clinician and patient during corrective speech therapy using dynamic palatography may expedite results with cleft palate patients in the speech clinic when implemented in a carefully structured treatment plan.
Articulation Disorders↗
Changing pattern of age-specific prevalence of hepatitis B surface antigen and corresponding antibody in Japan.
During the period 1978-1984 in Japan, the prevalence of hepatitis B surface antigen (HBsAg) in age groups below age 15 years was 18/2,550 (0.7%), and it was particularly low in the group below age 5 years (2/706 (0.3%)). The low prevalence of HBsAg in children under 15 years of age contrasted sharply with the much higher prevalence in persons age 15 years and older (36/2,050 (1.8%)). In accord with this, the prevalence of antibody to hepatitis B surface antigen (anti-HBs) was much lower in children below age 15 years than that in persons 15 years of age and older (29/2,550 (1.1%) vs. 242/2,050 (11.8%)). Furthermore, the prevalence of hepatitis B viral markers in 1978-1984 was lower than that during the period from 1972-1977 in every age group. A total of 13 (81%) of 16 mothers of carrier children, identified in 1978-1984, were positive both for HBsAg and hepatitis B e antigen in their sera. Now that mother-to-baby transmission appears to be the main route for establishing the persistent carrier state, its interruption should reduce the reservoir of hepatitis B virus, toward its eventual eradication, in Japan.
Adolescent↗
Histological distribution of MTV antigen in mice detected by immuno-peroxidase staining.
Histological localization of mammary tumor virus (MTV) antigen was investigated using a variety of organs high (DD/Tbr, SHN, SLN, GR) and low (BALB/c) mammary cancer mice strains and immuno-peroxidase staining with MTV antigen. Except for BALB/c strain mice, the mammary gland and mammary tumors were generally positive. Accessory male genital organs including the prostate, seminal vesicle, and coagulating gland also demonstrated a positive reaction, but the testis and female genital organs including uterus and ovaries did not. MTV antigen was also revealed in the serous acini of the salivary gland in both sexes. The site of positive reaction in the accessory male sex organs and salivary gland was located in the apical portion of the secretory epithelial cells and their secretory substance. Localization and intensity of antigenic expression of MTV detected histologically were comparable to results obtained by immunodiffusion test and radioimmunoassay. These evidences support the idea that MTV is transmitted horizontally via seminal fluid or saliva.
Animals↗
Pancreatic carcinoma in childhood.
A case of pancreatic carcinoma in a 14-year-old Japanese boy is reported. He complained of general fatigue, anorexia, abdominal distension, and abdominal mass. At autopsy, a whitish tumor was found from the head to the body of the pancreas. Metastasis was found in the liver, lungs, gall bladder, and various lymph nodes such as stomach, hilus, and periaorta. The tumor was histologically determined to be moderately differentiated adenocarcinoma (cribriform type) of duct cell origin. However, the tumors showed PAS-positive diastase-resistant mucus in the cytoplasm. Histocytology showed the positivity for alpha 1-antitrypsin, secretory component (sc), and CEA, but no S-amylase was detected in the cytoplasm. Electron microscopy revealed zymogen-like granules in the cytoplasm suggesting acinar differentiation.
Adolescent↗
Establishment of monoclonal antibodies reactive with epithelial and myoepithelial cells in the breast.
Monoclonal antibodies which are considered to be able to differentiate epithelial and myoepithelial cells in the breast have been developed. Human mammary carcinoma cell line (HBC-4W) was used for immunization. Monoclonal antibodies-B4B2F10 (epi-1), E9E8B7 (myo-1)-with IgM was examined using tissues from diseased breast by avidin-biotin-peroxidase assay. Epi-1 antibody reacted with epithelial cells while myo-1 antibody reacted with myoepithelial cells in the mammary glands, respectively. The reaction was markedly visible, in particular, in fibroadenoma, mastopathy, and papilloma, which showed clear two-cell-type structures. In the infiltrating ductal carcinoma, epi-1 antibody reacted with carcinoma cells, while myo-1 antibody reacted with stromal cells rather than carcinoma cells suggesting that infiltrating ductal carcinoma was mainly of epithelial origin. In the infiltrating lobular carcinoma, however, myo-1 as well as epi-1 antibodies reacted with carcinoma cells. It is suggested that infiltrating lobular carcinoma was of a mixture of epithelial and myoepithelial cell origin.
Adenofibroma↗
Mycosis fungoides and Sézary's syndrome show distinct histomorphological features.
A light microscopic investigation of skin biopsy specimens from 10 patients with plaque stage mycosis fungoides (MF) and from 6 with Sézary's syndrome (SS) was carried out according to the defined histologic criteria, for the purpose of detecting some morphological characteristics of these diseases for their histological differentiation. This study revealed that some histomorphological differences regarding the epidermal and dermal changes, epidermotropism and the cellular infiltrate existed between MF and SS, and that these diseases were two distinct entities showing differences not only from a clinical and hematologic but also from the histological viewpoint.
Adult↗
Pseudopelade of Brocq.
41 cases with scarring alopecia seen from 1979 to 1983 were analyzed and differentiated. After exclusion of 7 cases with lichen planopilaris, of 5 cases with discoid lupus erythematosus, of 2 cases with scleroderma, and of 1 case with folliculitis decalvans, there remained 26 cases. The clinical histological and direct immunofluorescence (DIF) findings in these patients suggest that pseudopelade of Brocq might be a distinct disease unrelated to other known types of scarring alopecia. The histopathology is characteristic, and shows the following features: little or only moderate lymphocytic infiltrate, absence of significant follicular plugging, and absence or decrease of sebaceous glands. DIF is negative, occasionally only IgM can be found at the basement membrane. The course of the disease is slowly progressive (in spite of little or no visible erythema), becoming eventually stationary after several years and resulting in a more or less severe permanent hair loss.
Adolescent↗
[Electrophysiological effects of bunaftine, an antiarrhythmic drug, on action potential characteristics in ventricular muscle preparations].
The electrophysiological effects of bunaftine were studied using the glass microelectrode technique. Bunaftine at 1, 5 and 10 mg/l produced a concentration-dependent depression of the maximum rate of rise of the action potential in guinea pig papillary muscle preparations without affecting the resting membrane potential and the action potential amplitude. The action potential duration (APD50, APD90) was significantly prolonged by the treatment with 1 and 5 mg/l bunaftine, while it was not changed by the treatment with 10 mg/l. The absolute refractory period (ARP) was also prolonged dose-dependently by the treatment of bunaftine; It was excessively prolonged (177% of control) at the concentration of 10 mg/l. Disopyramide produced similar electrophysiological changes to those of bunaftine except for the prolongation of ARP. ARP/APD90 ratio was significantly increased by bunaftine, but not by disopyramide. These electrophysiological effects of bunaftine and disopyramide observed in guinea pig ventricular preparations were similarly found in canine ventricular muscle preparations. These results indicate that the electrophysiological characteristics of bunaftine are similar to those of disopyramide in that the most prominent effect was the prolongation of ARP.
Action Potentials↗