The activity of S-4661, a new parenteral carbapenem antibiotic, was evaluated against 202 recent clinical isolates of respiratory pathogens. S-4661 was similar to or 2 times more active than imipenem, meropenem, and biapenem, and 8-128 times more active than ceftazidime against gram-positive bacteria. Against gram-negative bacteria, S-4661 was slightly less active than meropenem, but 2-8 times more active than the other agents. In particular, against Pseudomonas aeruginosa S-4661 showed the most potent activity. Thus it was found that S-4661 possesses a potent and well-balanced activity against respiratory pathogens.

Anti-Bacterial Agents↗

PubMedDate not supplied

Production of hydrogen peroxide and methionine sulfoxide by epigallocatechin gallate and antioxidants.

Epigallocatechin gallate (EGCG) induced apoptosis-associated characteristics in human oral tumor cell lines more efficiently than ascorbates, gallic acid, vitamin K, flavonoids or steroidal saponins. Since catalase partially inhibited the cytotoxic activity of EGCG, the possible involvement of hydrogen peroxide (H2O2) in cell death induction was investigated, using TCPO chemiluminescence method. Production of H2O2 by EGCG, sodium ascorbate, gallic acid or catechin reached a maximum level within 30 minutes, and was increased up to a plateau level above pH 8. Under optimal conditions, 1 mM EGCG was converted to 1 mM H2O2. At neutral pH, EGCG produced the highest amount of H2O2, followed by gallic acid, sodium ascorbate and catechin. EGCG produced methionine sulfoxide from methionine in the culture medium, while the methionine oxidation by EGCG was significantly reduced in the presence of serum. ESR spectroscopy showed that EGCG, gallic acid and sodium ascorbate, but not catechin, produced radicals under alkaline condition and that all these compounds scavenged superoxide anion, produced by hypoxanthine-xanthine oxidase reaction. EGCG also effectively scavenged the ascorbate and gallate radicals, more efficiently than other compounds. These data suggest that the apoptosis induction by EGCG may be mediated by H2O2 produced in the culture medium.

Antineoplastic Agents↗

PubMedDate not supplied

Induction of tumor degeneration by sodium benzylideneascorbate.

Intravenous administration of sodium benzylideneascorbate (SBA) rapidly necrotized inoperable human lung cancer, and induced degeneration of 3'-methyl-4-dimethylaminoazobenzene-induced rat hepatocellular carcinoma (vacuolar, eosinophilic degeneration, nuclear debris) without affecting the serum glutamic oxaloacetic transaminase, gamma-glutamyl transpeptidase and total protein levels. Cultured normal human lung and skin fibroblasts, and human glioma and glioblastoma cell lines were relatively resistant to SBA, when compared to human myelogenous leukemic cell lines. SBA had no apparent host immunopotentiation activity such as stimulation of cytokine action or production; activation of monocyte or polymorphonuclear cells; or modulation of poly (ADP-ribose) glycohydrolase activity. The data suggest that the antitumor activity of SBA might be produced by direct action of authentic SBA or its metabolized form(s), rather than by immunopotentiation of the hosts.

Animals↗

PubMedDate not supplied

Increased expression of the proto-oncogene, c-myc, in human neuroblastoma cells by reversible inhibition of cell growth.

Expression of the proto-oncogenes N-myc and c-myc in the human neuroblastoma cell line, IMR32, was examined after reversible inhibition of DNA synthesis by treatment with deferoxamine. After 48 h treatment with 10(-5) M deferoxamine, the number of c-myc expressing cells doubled, while N-myc expressing cells did not change. The expression level of c-myc in each cell also increased. These results suggested that the synthesis of cellular factor(s) involved in the degradation of c-myc RNA or its product was suppressed by reversible inhibition of cell growth. The regulatory mechanisms of expression of N-myc and c-myc may be distinct.

Cell Cycle↗

PubMedDate not supplied

Two histologic types of early gastric carcinoma and their cytologic presentation.

A study was made of 119 case of early gastric carcinomas as to age, sex, histologic cell types, depth of penetration of the cancer, metastasis to the regional lymph nodes and cellular changes of the mucosa near the foci of center. Two distinctly different cellular types were identified. One was the intestinal type, and the other was a diffusely infiltrated, mixed-cell type that was termed the "gastric" type. In both sexes, the intestinal type occurred in the older age group while the gastric type was noted in the younger age group. Once the cancer had penetrated through the muscularis mucosae, there was a sudden, increased incidence of metastasis to the regional lymph nodes regardless of the cellular type. While still confined to the mucosae, only one case of early gastric carcinoma, one of the gastric type, had metastasized to the regional lymph nodes. On this histologic basis, cytologic characteristics of two types of gastric carcinoma are summarized, and the importance of their recognition is emphasized.

Adenocarcinoma↗

PubMedDate not supplied

Diagnostic pitfalls in cerebrospinal fluid cytology.

Four types of cells that may be the source of important diagnostic pitfalls in cerebrospinal fluid cytology are presented: (1) nucleus pulposus cells, (2) keratinized squamous cells from craniopharyngioma and sphenoid sinus carcinoma, (3) reactive leptomeningeal cells and (4) epitheloid cells from sarcoidosis. For each the cellular morphology is described and representative clinical, cytologic and histologic presentations are discussed.

Adult↗

PubMedDate not supplied

Suppression of HL-60 cell proliferation by deferoxamine: changes in c-myc expression.

Deferoxamine, an iron chelating agent, inhibits growth of HL-60 cells in a dose-dependent fashion. This inhibition of proliferation was completely blocked by simultaneous addition of equal molar FeCl3, and FeCl3 added after 24 hours of deferoxamine treatment was also effective. After 48 hrs, however, the delayed addition failed to reverse growth inhibition by deferoxamine. We showed that deferoxamine-treated HL-60 cells become arrested in S phase rather than at G1/0 phase. Changes in c-myc expression were examined in these deferoxamine-treated cells. A rapid decline of c-myc RNA expression was followed by increased expression (1.6-fold over untreated controls). Similar results were obtained when the expression of c-myc protein was evaluated. These changes in c-myc expression may be involved in the growth inhibition of HL-60 cells by deferoxamine. These results are contrasted with the effects of the differentiation inducer, 1 alpha,25(OH)2D3.

Cell Cycle↗

PubMedDate not supplied

Induction of DNA fragmentation by tannin- and lignin-related substances.

A variety of tannin and lignin-related compounds were compared for their ability to induce nucleosome-sized DNA fragmentation (a biochemical hallmark of apoptosis), using agarose gel electrophoresis and a fluorescence activated cell sorter. Monomeric, dimeric, trimeric and tetrameric hydrolysable tannins induced nucleosome-sized DNA fragmentation in HL-60 cells, more potently than condensed tannins. The highest activity was detected in gallic acid, a component unit of tannins. Natural lignified materials, except for caffeic acid and its dehydrogenation polymer, showed much weaker activity. Protein-bound polysaccharide (PSK) was inactive. Gallic acid induced DNA fragmentation in four human myelogenous leukaemic cell lines, but not in human T-cell leukaemia and erythroleukaemia cell lines. Ca2+ depletion from the culture medium slightly, but significantly, reduced the apoptosis-inducing activity of gallic acid, but did not significantly affect that of tannic acid or caffeic acid. After treatment with gallic acid, intracellular Ca2+ concentration was significantly elevated. The apoptosis-inducing activity of polyphenols may further emphasize their medicinal efficacy.

Apoptosis↗

PubMedDate not supplied

Induction of DNA fragmentation in human myelogenous leukaemic cell lines by phenothiazine-related compounds.

A series of phenothiazine, benzo[a]phenothiazine and benz[c]acridine derivatives were compared for their ability to induce nucleosome-sized DNA fragmentation (a biochemical hallmark of apoptosis), using agarose gel electrophoresis and a fluorescence activated cell sorter. Significant DNA fragmentation-inducing activity was detected in 12H-benzo[a]phenothiazine, 5-oxo-5H-benzo[a]phenothiazine and 9-methyl-12H-benzo[a]phenothiazine, which induced the monocytic differentiation of human myelogenous leukaemic cell lines. On the other hand, an other three benzo[a]phenothiazines, six 10-[n-(phthalimido)alkyl]-2-substituted-10H-phenothiazines, six 1-(2-chloroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alkyl-1- ureas, and twelve benz[c]acridines showed little or no DNA fragmentation-inducing activity. Active benzo[a]phenothiazines induced DNA fragmentation in four human myelogenous leukaemic cell lines (HL-60, ML-1, U-937, THP-1), but not in human T-cell leukaemic MOLT-4 and erythroleukaemic K-562 cell lines, which were also resistant to other apoptosis-inducing agents. Ca2+-depletion from the culture medium did not significantly affect their DNA fragmentation-inducing activity. The differentiation and apoptosis-inducing activity of benzo[a]phenothiazines have an important role for their medicinal efficacy.

Acridines↗