Apoptosis supercedes necrosis in mitochondrial DNA-depleted Jurkat cells by cleavage of receptor-interacting protein and inhibition of lysosomal cathepsin

In the present study, we used mitochondrial DNA-depleted Jurkat subclones (rho0 cells) to demonstrate that Fas agonistic Ab (CH-11), at the concentrations that evoke apoptotic death of the parental Jurkat cells, induced necrosis mainly through generation of excess reactive oxygen species, lysosomal rupture, and sequential activation of cathepsins B and D, and in minor part through activation of receptor-interacting protein (RIP). In the rho0 cells treated with CH-11, ATP supplementation converted necrosis into apoptosis by the formation of the apoptosome and subsequent activation of procaspase-3. In these ATP-supplemented rho0 cells (ATP-rho0), generation of excess ROS and lysosomal rupture were still seen, yet cathepsins B and D were inactivated and RIP was degraded. The conversion of necrosis to apoptosis, RIP degradation, and cathepsin inactivation in ATP- rho0 cells were blocked by caspase-3 inhibitors. Activities of cathepsins B and D in the lysate of necrotic rho0 cells were inhibited by the addition of apoptotic parental Jurkat cell lysate. Thus, apoptosis may supercede necrosis.     

Immunotherapy with bestatin for acute nonlymphocytic leukemia in adults

Summary In a cooperative randomized control study of immunotherapy with bestatin in combination with chemotherapy in adults with acute nonlymphocytic leukemia (ANLL), 101 patients (48 in the bestatin group and 53 in the control group) out of 115 patients registered were evaluated as eligible. The bestatin group achieved a statistically significant prolongation of survival compared with the control group in overall ANLL and acute myelogenous leukemia. In the analysis of patient age, the bestatin group achieved a statistically significant prolongation of both the remission duration and survival in patients aged 50 to 65 years, while the differences were not significant in the 15 to 49 age group. The bestatin group tended to achieve a higher rate of reinduction of remission in patients who had recurrence of leukemia. Side effects developed in only 5 (9.6%) of 52 patients treated with bestatin. None of these side effects were particularly serious in nature. It is concluded that bestatin is useful for prolongation of survival of adult patients with ANLL, making for a longer remission duration especially in elderly patients and with few side effects.     

Two monoclonal antibodies against small-cell lung cancer show existence of synergism in binding

Summary Murine IgG1 monoclonal antibodies (mAbs), ITK-2 and ITK-3, were generated against a small-cell lung cancer (SCLC) cell line. Enzyme-linked immunosorbent assay using a variety of established cell lines as substrates, immunoperoxidase staining of freshly frozen tissue sections, and fluorescence-activated cell sorter analysis of peripheral blood leukocytes showed that these mAbs recognize a part of the SCLC-associated cluster 1 antigen. In immunoprecipitation studies, both ITK-2 and ITK-3 bound to a 145-kDa glycoprotein of SCLC cell membrane extracts, as did MOC-1 and NKH-1, which both recognize the cluster 1 antigen. However, because the binding of¹²⁵I-labeled ITK-2 to SCLC cells was not inhibited by MOC-1 or NKH-1, the binding site of ITK-2 on SCLC cells appeared to be different from that of either MOC-1 or NKH-1. Unexpectedly, binding of¹²⁵I-labeled ITK-2 to SCLC cells increased in the presence of ITK-3. This ITK-3-induced increase in ITK-2 binding was due partly to an increase in the number of binding sites for ITK-2 on SCLC cells. Addition of ITK-3 may, therefore, improve the effectiveness of ITK-2-based tumor detection or therapy.     

The Purification of a GroEL-Like Stress Protein from Aerobically Adapted Campylobacter jejuni

From plate cultures of Campylobacter jejuni grown in room air a particulate protein of 62 kDa was isolated by ion-exchange chromatography. The protein had a square shape from the side view but when viewed from the top it had a star-shaped structure. The molecular size of the whole particle determined by gel filtration was 850 kDa which suggested the presence of 14 subunits of 62 kDa in each particle. The N-terminal 37 amino residues showed more than 80% homology with the sequence of these heat shock protein (HSP) 60 homologs of Chlamydia trachomatis, Helicobacter pylori, and Escherichia coli (GroEL). This protein is immunologically cross-reactive with the antiserum for the 60-kDa HSP of Yersinia enterocolitica. Production of the 62-kDa protein increased under heat stress and growth in an aerobic atmospheric environment. From these observations we concluded that the 62-kDa protein is a Campylobacter stress protein (Cj62) which belongs to the HSP 60 family.     

Molecular cloning of the gene which encodes beta-N-acetylglucosaminidase from a marine bacterium, Alteromonas sp. strain O-7.

The gene encoding the periplasmic beta-N-acetylglucosaminidase (GlcNAcase B) from a marine Alteromonas sp. strain, O-7, was cloned and sequenced. The protein sequence of GlcNAcase B revealed a highly significant homology with Vibrio GlcNAcase and alpha- and beta-chains of human beta-hexosaminidase.     

Impact of long-term continuous positive airway pressure on liver fat in male obstructive sleep apnea patients with fatty liver

Sleep and Biological Rhythms - Obstructive sleep apnea (OSA) is an established factor in the pathogenesis and exacerbation of fatty liver disease. However, randomized controlled trials have failed...     

The human interleukin-10 receptor gene maps to chromosome 11q23.3

The human interleukin-10 receptor (IL-10R) gene has previously been mapped to chromosome 11. Here, we have determined the precise location of the human IL-10R gene by the fluorescence in situ hybridization method, and have found that the IL-10R gene maps to chromosome 11q23.3.     

Clinical Isolate of Pseudomonas aeruginosa that Degrades Salicylate by the ortho Pathway

A clinical isolate of Pseudomonas aeruginosa was found capable of utilizing salicylate by the salicylate hydroxylase and β-ketoadipate pathway.