Relationship between phagocytosis and immunoglobulin A release from human colostral macrophages.

Macrophages and neutrophils that contain mainly secretory immunoglobulin A (IgA) comprise the majority of cells in human colostrum. These cell populations were separated and analyzed for their ability to release total IgA and secretory IgA when stimulated to phagocytose. Colostral macrophages phagocytosed opsonized bacteria and nonopsonized latex particles; at the same time, IgA was released. Neutrophils poorly phagocytosed opsonized bacteria but actively phagocytosed latex particles. In contrast to the macrophages, the neutrophils did not release IgA, even after active phagocytosis of latex. Consequently, colostral macrophages are the main source of IgA released from colostral leukocytes when these cells are exposed to organisms or particles that are phagocytosed. A function for colostral neutrophils which sequester IgA is proposed.     

Hepatitis B surface antigen particles of subtypes adw and adr, and compound subtype (adwr) in symptom-free carriers in Japan.

Of sera from 1,878 Japanese blood donors who carried hepatitis B surface antigen (HBsAg), 420 were subtyped as adw (22.4%) and 1,443 as adr (76.8%); only 15 (0.8%) contained HBsAg of subtype ayw or ayr. Sera with HBsAg/adr had higher HBsAg titres than those with HBsAg/adw (geometric mean of haemagglutination titre: 10.1 +/- 2.4 vs. 9.7 +/- 2.4, p less than 0.01), and a higher prevalence of hepatitis B e antigen (24% vs. 13%, p less than 0.001). Carriers of HBsAg/adr progressively predominated over those of HBsAg/adw with increasing age. Of sera from 1,863 carriers of HBsAg/adw or HBsAg/adr, 182 (9.8%) contained HBsAg particles with both subtypic determinants in the w/r allele. The presence of w and r determinants on the same particles was ascertained by sandwiching them between monoclonal antibody with the specificity for w and that with the specificity for r. HBsAg particles of compound subtype (adwr) were found more often in sera with hepatitis B e antigen than those without it (145/403 [36.0%] vs. 37/1,460 [2.5%], p less than 0.001). Sera with HBsAg/adwr particles had HBsAg titres higher than those without them (12.4 +/- 1.9 vs. 9.7 +/- 2.3, p less than 0.001). HBsAg/adwr particles arise from phenotypic mixing of the S-gene product of wild-type virus and that of mutants with point mutations for subtypic changes. The results obtained indicated that HBV strains of subtype adr have a higher replicative activity than those of adw, and suggested that mutations in the S gene for subtypic changes would be associated with an active replication of hepatitis B virus.     

Synthesis of antitumor-active conjugates of adriamycin or daunomycin with the copolymer of divinyl ether and maleic anhydride

Polymeric conjugates of adriamycin (ADR) ( 2 ) or daunomycin (DM) ( 3 ) were synthesized by reaction of the drugs with the copolymer of divinyl ether and maleic anyhdride (DIVEMA) ( 1 ). The content of ADR moieties in the DIVEMA conjugate ( 4 ) could be varied depending on the reaction conditions up to 35,8 wt.-%. Considering the low toxicity and the high possibility of renal excretion, DIVEMA with M?_w of 7000 and M?_w/M?_n = 1,6 was used for the conjugation. The rate of drug release from the conjugate was determined under physiological conditions by reversed phase HPLC. Within 14 days only 15% of the attached ADR was released from conjugate 4 . The antitumor activity of the conjugates was tested in vitro and in vivo against mouse P388 leukemia. Conjugate 4 proved to be 28 times less active than ADR in vitro, which could be explained from the slow drug-release. On the contrary 50% of the leukemic mice treated by 4 survived more than 60 days, whereas no mice given ADR alone or the admixture of ADR and DIVEMA survived 30 days. An antitumor activity of the polymeric conjugate better than that of the free drug was also observed in vivo with DM. Such a polymeric effect can be attributed either to the change in body distribution, the difference in pharmacokinetics, or the slow drugrelease.     

Immunohistochemical Investigation of Vimentin, Neuron-specific Enolase, α1-antichymotrypsin and α1-antitrypsin in Adenoid Cystic Carcinoma of the Salivary Gland

Fifty-four adenoid cystic carcinomas (ACC) arising in major and minor salivary glands as well as in normal salivary glands were studied by immunohistochemistry for the presence of vimentin, neuron specific enolase (NSE), α₁-antichymotrypsin (α₁-ACT) and α₁-_- antitrypsin (α₁-_- AT). Five patterns of histological differentiation were found in ACC, and for the cellular components of each, it was possible to establish a special immunohistochemical profile. In ACC, vimentin-positive cells were observed in the outer tubular, cyst-lining and small angular cells. NSE was positive in the myoepithelial cells of normal salivary gland. Neoplastic cells of ACC showed NSE positivity mainly in the small angular cells and partly in the duct luminal cells. α₁-ACT was localized in the intercalated duct cells and serous acinar cells of normal salivary gland, and in the duct luminal cells of ACC. α₁-AT could not be detected in any of the epithelial cells of normal salivary gland. In ACC, eosinophilic hyaline material in the cribriform spaces was positive for α₁-AT, but no positivity was demonstrated in tumor cells. The present study showed that there are at least two populations of tumor cells in ACC: duct luminal cells that express α₁-ACT, thus indicating their ductal character, and small angular cells that express vimentin, characteristic of non-luminal cells. Moreover, our results indicate that α₁-AT is a useful marker of basement membrane-like material.     

Clostridium perfringens foodborne outbreak due to braised chop suey supplied by chafing dish

On February 13, 2002, a public health center in Hiroshima Prefecture, Japan, was notified that many individuals living at the Japan Maritime Self-Defence Force base had symptoms resembling those of food poisoning. Self-administered questionnaires requesting information regarding meal consumption and symptoms were distributed to all 281 members at the base. A case of the illness was defined as a member who had had watery or mucousy stool, or loose stool with abdominal cramps, more than twice a day after consuming dinner on February 12. Control of the illness was defined as a member with no symptoms. The dinner on February 12 was significantly associated with the illness (Mantel-Haenszel odds ratio: 3.59, 95% confidence interval: 1.06-12.20). A case-control study showed that, among the food supplied at dinner on February 12, the braised chop suey was significantly associated with the illness (odds ratio: 12.30, 95% confidence interval: 1.90-521.00). The braised chop suey had been stored in a chafing dish. An environmental investigation indicated that Clostridium perfringens (C. perfringens) in the chafing dish proliferated under an inappropriate heat-retention temperature, and the contaminated braised chop suey could have caused the food poisoning. This study demonstrated that the recommended heat-retention temperature (over 65 degrees C) should be confirmed thoroughly.     

Anionic copolymerization of β-lactones in correlation with the mode of fission. studies on the syntheses of aliphatic polyesters. XI

The copolymerization behavior of β-propiolactone (PL) and α.α-bischloromethyl β-propiolactone (α-BCPL) is correlated with the mode of fission. With sodium acetate as catalyst, the formation of β-acetoxy propionic acid at the initiation reaction was observed and α-BCPL was more than five times as reactive as PL in copolymerization. Thus propagation by carboxylate anion through alkyl-oxygen fission was presumed in the case of pyridine and the acetate of Na, Li, and Mg as catalyst. On the other hand, the formation of ethyl β-hydroxy propionate and the decreased reactivity of α-BCPL in copolymerization was observed with magnesium and aluminum ethoxide as catalyst. In the case of the ethoxide of Na, Li, and Al, and Et₂Mg or Et₃Al as catalyst, propagation by alkoxide anions through acyl-oxygen fission of the coordinated lactones was presumed.     

The loss of subtypic determinants in alleles, d/y or w/r, on hepatitis B surface antigen

Hepatitis B surface antigen possesses the group-specific determinant called a and one or another member from each of two pairs of allelic determinants, d and y as well as w and r, thereby creating the four major subtypes, adw, adr, ayw and ayr. In the sequence of major surface antigen polypeptides made of 226 amino acid residues, lysine or arginine at amino acid position 122 specifies d or y determinant, and lysine or arginine at position 160 specifies w or r determinant, respectively. By means of site-directed mutagenesis and expression of mutant genes in cultured cells, the mechanism for the loss of subtypic determinants on surface antigens was investigated at the molecular level. A rare sample of surface antigen of subtype ad, devoid of w or r determinant, had asparagine at position 160. When it was converted to lysine, the surface antigen of subtype adw was obtained. Two samples of surface antigen were subtyped as ar. They lacked d determinant, despite having lysine at position 122 which usually specified it. They differed from all reported sequences of surface antigen in amino acid 144 or 145. They displayed d determinant when amino acid 144 was converted from glutamic acid to aspartic acid, or when amino acid 145 was changed from alanine to glycine. These results indicate that the key amino acid residue at position 122 or 160 is indispensable for the expression of subtypic determinants and that some distant residues are also crucially involved in conforming them.     

Tissue factor pathway inhibitor can interact with platelets

Tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of blood coagulation. However, there is no report on interaction between TFPI and platelets other than that by Tsuji, who found that whole blood anticoagulated with TFPI exhibited remarkable decrease in platelet count. Our study revealed that washed platelets suspended in modified Tyrode's buffer (8 mM CaCl2) containing TFPI exhibit platelet aggregation. However, platelets aggregation was observed without TFPI, but its increase and intensity were slow and weak, compared to that in the presence of TFPI. This aggregation was inhibited by anti-CD41 (anti-GPIIb) antibody. This finding suggested that TFPI promotes platelet aggregation.