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Biomedical subjects

T Azuma

Publications and source records attributed to T Azuma.

At least 73 records · Page 4Linked to original sources
PubMed1989

Gastrin is a major mediator of the gastric phase of acid secretion in dogs: proof by monoclonal antibody neutralization.

We developed a monoclonal antibody, 28.2, that binds specifically to the amidated carboxyl terminal region common to gastrin and cholecystokinin. This immunoglobulin G1 antibody has high affinity (ID50 = 30-70 pM for gastrin and cholecystokinin peptides), binds labeled gastrin similarly at 37 degrees C and 4 degrees C, and shows minimal inhibition of binding in the presence of 40% canine serum. Antibody 28.2 was used to carry out in vivo immunoneutralization studies in 8 dogs previously prepared with chronic gastric fistulas. Preliminary studies revealed that a single intravenous dose of 0.75 mg of partially purified immunoglobulin G of monoclonal antibody 28.2 completely inhibited the acid stimulatory effect of exogenous gastrin-17 given intravenously at 200 pmol/kg.h, a physiologic dose, and inhibited by 70% the acid response to a supraphysiologic dose, 800 pmol/kg.h. The same dose of antibody decreased the acid secretory response obtained during distention of the stomach with 300 ml of 5.8% glucose solution by 98% and decreased the response to distention with 300 ml of 8% peptone solution by 68%. A 10-fold higher dose of antibody decreased the acid response to peptone by 96%. The gastrin antibody had no effect on the acid response to exogenous histamine. A control antibody, specific for the biologically inactive glycine-extended gastrin/cholecystokinin peptapeptide region, had no significant effect on gastric acid secretion stimulated by gastrin or by gastric distention with nutrients. These studies indicate that circulating gastrin is of major importance in the gastric phase of gastric acid stimulation caused by distention of the stomach with nutrients.

Animals↗
PubMed1989

Human pepsinogen C (progastricsin) polymorphism: evidence for a single locus located at 6p21.1-pter.

A series of six clones containing the entire human pepsinogen C gene (PGC) was identified in a cosmid vector library by using cDNA and oligonucleotide probes. The 10.7-kb PGC gene includes nine exons and exhibits a high degree of sequence identity (60%) with the functionally related pepsinogen A genes. The predicted amino acid sequence was identical with the partial amino-terminal and carboxyl-terminal sequences of purified pepsinogen C. An informative restriction fragment length polymorphism was detected with several restriction enzymes and involved an insertion or deletion of 100 bp of intron sequence located between exons 7 and 8. Evidence that there is only a single PGC gene in humans is presented. The PGC gene and the prolactin gene were regionally localized to 6p21.1-pter by analysis of mouse X human somatic cell hybrids.

Amino Acid Sequence↗
PubMed1989

Experimental drug-induced allergic nephritis mediated by antihapten antibody.

Experimental drug-induced allergic nephritis (DIAN) was mediated by an antihapten antibody. It has been postulated that DIAN is induced by cellular and humoral mechanisms. We tried to induce DIAN in mice, where the mechanism depends on humoral immunity. The first attempt was made in mice actively producing antibodies against cephem antibiotics, i.e. cephalothin (CET). Acute interstitial nephritis (AIN), morphologically similar to human disease, was obtained by injection of a CET-protein conjugate into the renal cortex in mice producing anti-CET-IgE and IgG antibodies. AIN could also be induced when normal mice, passively given anti-CET IgG antibody, received a subsequent intrarenal challenge with CET-protein conjugate. These preliminary results indicate that IgG antibody has an important role in the genesis of DIAN. Further experiments were performed with monoclonal antibodies directed against haptens instead of antibiotics in order to clarify the Ig isotype concerned. In mice passively given anti-Dansyl-IgG2a or anti-NP-IgG2a monoclonal antibodies, a challenge with an appropriate hapten-protein conjugate into the renal cortex resulted in AIN. However, transfer of anti-Dansyl-IgE or anti-DNP-IgE monoclonal antibodies, followed by challenge, did not induce AIN. In the experimental systems described, the involvement of a cellular immune mechanism is excluded. The results suggest that IgG, but not IgE antibody, is essential for the induction of DIAN by humoral immune mechanism.

Animals↗
PubMed1989

[The effect of sofalcone on the kinetics of the generative cells and superficial epithelial cells in mouse gastric mucosa].

Effects of an anti-ulcer drug, 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy) chalcone (sofalcone), on the generative cells and kinetics of superficial epithelial cells in mouse gastric mucosa, including the effect of hydrocortisone on them, were investigated by the use of 3H-thymidine autoradiography. The labeling indices and the width of the generative cell zone in the fundic mucosa were significantly decreased by administration of hydrocortisone. The decrease in the labeling indices and the width of the generative cell zone induced by administration of hydrocortisone were not inhibited by sofalcone. Hydrocortisone had no significant influence on the labeling indices of the generative cell zone in the pyloric mucosa, but decreased the width of it. The decrease in the width of the generative cell zone induced by hydrocortisone was inhibited by sofalcone. Concerning the influence on the kinetics of superficial epithelial cells, hydrocortisone inhibited the increase in the labeling indices of the superficial epithelial cells after continuous administration of 3H-thymidine in both the fundic mucosa and pyloric mucosa. In the fundic mucosa, sofalcone showed no influence on the inhibition by hydrocortisone, but in the pyloric mucosa, the effect of hydrocortisone was abolished by sofalcone. These results suggest that sofalcone inhibits the reduction of the cell production and the prolongation of the life span of superficial epithelial cells caused by hydrocortisone in the pyloric mucosa.

Animals↗
PubMed1989

Fluorescent histochemical study on the localization of myofibroblasts in the healing of acetic acid-induced gastric ulcers in the rat.

The changes in the localization of FITC-phalloidin-positive smooth muscle cells and interstitial cells were studied in control and acetic acid-treated rat fundic mucosae. In the control rats, the FITC-phalloidin-positive cells mostly corresponded to smooth muscle cells of the muscularis mucosae, and arteriolar and venular smooth muscle cells. On the other hand, the fluorescence of the smooth muscle cells of the muscularis mucosae disappeared and a large number of fluorescent interstitial cells appeared in the regenerated mucosal layer in rats one week after the acetic acid-treatment, while three weeks after the application, severely thickened fluorescent muscularis mucosae were formed.

Acetates↗
PubMed1989

[The effect of chemical sympathectomy on the cell kinetics of gastric mucosa in golden hamsters].

The effects of chemical sympathectomy on the differentiation of the generative cells, superficial epithelial cells and gastrin cells of the gastric mucosa of hamster were examined by 3H-thymidine autoradiography. The labeling indices of the generative cell zone in the gastric mucosa and antral gastrin cells showed a transient significant decrease after chemical sympathectomy, and then they were gradually restore with time. After 4 weeks onward, the labeling indices of the generative cells showed a slightly low value compared with those in controls. The renewal of superficial epithelial cells and gastrin cells was examined in the hamster sympathectomized for 4 weeks. The time required for the differentiation to PAS positive superficial epithelial cells or gastrin cells had a tendency to elogate after chemical sympathectomy. These results suggest that chemical sympathectomy played an inhibitive action on the proliferation and the differentiation of gastric mucosa.

Animals↗
PubMed1989

Application of new silicone gel to sustained release dosage form of antitumor drug.

The object of this study was to develop a sustained release implantable dosage form of a new silicone gel (PHYCON 6600R) which undergoes addition polymerization to produce a solid gel at ordinary temperature. Implantable PHYCON-drug composites were studied as a means of tumor therapy using 3',5'-diesters of 5-fluoro-2'-deoxyuridine (FUdR-Cn) as a model for antitumor drugs. Using an in vitro dissolution test, we found that the release characteristics of drugs from these preparations could be controlled by the addition of powdered L-alanine. In vivo studies of antitumor activity were carried out, using preparations containing the dodecyl ester (FUdR-C12) by measuring the lifespan of lymphoma-inoculated mice. Antitumor activity, reflected in increased lifespan, was shown to be greater following intraperitoneal administration of the PHYCON formulations (drug and L-alanine) than following injections of the drug alone. Our results suggest that sustained release implantable formulations of antitumor drugs in PHYCON might be suitable for tumor chemotherapy.

Animals↗
PubMed1989

Application of PHYCON 6600 to achieve sustained release of an antitumor drug (carmofur).

This study attempted to develop sustained release implantable dosage forms based on PHYCON 6600, a new silicone gel. The solid gel is prepared at ambient temperature by polymerization of two basic components (PHYCON A and PHYCON B solutions) for about 1 h. The application we explored was the use of implantable PHYCON-drug composites in tumor therapy. Carmofur (1-hexylcarbamoyl-5-fluorouracil, HCFU) was chosen as a practical antitumor drug. Using an in vitro dissolution test, near zero-order release rate was observed over a period of about 35 days. The amount of drug released by the 'burst phenomenon' was found to be less than the HCFU toxic dose. In vivo studies of antitumor activity were carried out by measuring the lifespan of lymphoma-inoculated mice (ILS). The increase in lifespan (38.5%) following intraperitoneal administration of the PHYCON formulations was similar to that (36.4%) following injection of the drug alone for 5 days. Our results suggest that the injectable and implantable sustained release formulations of the antitumor drug in PHYCON might be suitable for tumor chemotherapy.

Animals↗
PubMed1989

Effect of daily energy expenditure on the creatinine clearance and daily urinary protein excretion of patients with mesangial proliferative glomerulonephritis.

In the present study, the relationships among daily energy expenditure, renal function (creatinine clearance, Ccr), and daily urinary protein excretion were examined. In total, 104 adult patients (from 9 renal clinics in Japan) with primary chronic glomerulonephritis were fitted with a portable calorie counter for about two weeks to estimate their daily energy expenditure. On two separate days when the energy expenditure was expected to be contrastingly different, urine collection and blood sampling were performed, and the Ccr and daily urinary protein excretion were determined. Multiple regression analysis of Ccr clearly demonstrated a significant correlation between its acceleration and increase in the daily protein intake or protein excretion. In mesangial proliferative glomerulonephritis showing a constant level of protein intake, the enhancement of Ccr revealed a significant inverse relation to the increase in daily energy expenditure (%BMR). It was demonstrated statistically that a daily energy expenditure exceeding 150 %BMR slowed the Ccr down. This limit was almost the same as the level in healthy adults living in urban cities of Japan. The urinary protein excretion was significantly correlated with the daily protein intake. These results should be taken into consideration in prescribing for each individual patient an allowable degree of labor or any other activity and an adequate dietary regimen, and also in evaluating the efficacy of a drug for glomerulonephritis.

Adolescent↗
PubMed1989

[Ontogeny of pancreatic gastrin cells in neonatal rat].

It is well known that gastrin immunoreactive cells are observed in the fetal and postnatal rat pancreas. The role of the gastrin cells is unknown, however, it has been suspected that pancreatic gastrin may influence the development of pancreas and the gastrointestinal tract. The present study shows the localization of pancreatic gastrin cells and the ability of auto-proliferation of them in development. Gastrin cells were seen in 0-d to 2-wk-old rats in islet and in 0-d to 4-wk-old rats among exocrine cells. The ratio of gastrin cells to islet cells decreased in neonatal development and in rats older than 14-d gastrin cells were never observed in islet. Labeling indices of pancreatic gastrin cells after one injection of tritiated thymidine were 2.6% to 4.6% for 10 days after birth. It was suggested that gastrin cells have the ability of autoproliferation for 10 days after birth.

Age Factors↗
PubMed1988

Characterization of the combining site of mouse myeloma protein M315.

The interaction of M315 with 2,4-dinitrophenyl haptens was studied. 2,4-Dinitroaniline (DNP-NH2) showed maximum affinity to M315 at about pH 4. The pH dependence of the association constant of DNP-NH2 to M315 showed three transitions at pH 4.7, at pH 7.2, and below pH 9, respectively. Since the DNP-NH2 molecule has no charged group in this pH range, the transitions were explained in terms of amino acid residues with ionizable side chains in M315. Judging from the pK values and the effect of succinylation, these transitions were concluded to be related to ionizations of carboxyl, imidazole, and phenol groups, respectively. Measurement of the fluorescence of affinity-labeled M315 suggested that the transition at pH 4.7 reflected an equilibrium between two forms of M315 with different conformations of the combining site. The contribution of the amino acid sequence on the light (L) chain to the interaction with haptens was studied by use of antibodies (Abs) reconstituted from the heavy chain of M315 (H315) and either a homologous or a heterologous L chain. The reconstituted heterologous Ab (H315L952) showed similar pH dependence of binding to DNP-NH2 to that of the homologous Ab (H315L315). Moreover, the two Abs showed no appreciable difference in binding to DNP-haptens of different sizes. These results suggested that the difference in the amino acid sequences of L315 and L952, which originated by a somatic hypermutation, has little effect on the ligand binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗
PubMed1988

Property of class I H-2 alloantigen-reactive Lyt-2+ helper T cell subset. Abrogation of its proliferative and IL-2-producing capacities by intravenous injection of class I H-2-disparate allogeneic cells.

The present study investigates the distinctiveness of Class I H-2 alloantigen-reactive Lyt-2+ helper/proliferative T cell subset in the aspect of tolerance induction. Primary mixed lymphocyte reactions (MLR) revealed that Lyt-2+ and L3T4+ T cell subsets from C57BL/6 (B6) mice were exclusively capable of responding to class I H-2 [B6-C-H-2bm1 (bm1)]- and class II H-2 [B6-C-H-2bm12 (bm12)]-alloantigens, respectively. Anti-bm12 MLR was not affected by i.v. injection of bm12 spleen cells into recipient B6 mice. In contrast, a single i.v. administration of bm1 spleen cells into B6 mice resulted in the abrogation of the capacity of recipient B6 spleen and lymph node cells to give anti-bm1 MLR. This suppression was bm1 alloantigen-specific, since lymphoid cells from B6 mice i.v. presensitized with bm1 cells exhibited comparable anti-bm12 primary MLR to that obtained by normal B6 lymphoid cells. Such tolerance was rapidly (24 h after the i.v. injection of bm1 cells) inducible and lasting for at shortest 3 wk. Addition of lymphoid cells from anti-bm1-tolerant B6 mice to cultures of normal B6 lymphoid cells did not suppress the proliferative responses of the latter cells, indicating that the tolerance is not due to the induction of suppressor cells but attributed to the elimination or functional impairment of anti-bm1 proliferative clones. The tolerance was also demonstrated by the failure of tolerant lymphoid cells to produce IL-2. It was, however, found that anti-bm1 CTL responses were generated by tolerant lymphoid cells which were unable to induce the anti-bm1 MLR nor to produce detectable level of IL-2. These results demonstrate that class I H-2 alloantigen-reactive Lyt-2+ Th cell subset exhibits a distinct property which is expressed by neither Lyt-2+ CTL directed to class I H-2 nor L3T4+ Th cells to class II H-2 alloantigens.

Animals↗