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Biomedical subjects

E George

Publications and source records attributed to E George.

At least 109 records · Page 6Linked to original sources

Induction of SCE by indirect mutagens in cultured rat hepatoma cells and in Chinese hamster V79 cells co-cultivated with hepatocyte primary cultures.

The continuous rat hepatoma cell line H4IIEC3/G- and rat hepatocyte primary cultures (hpc) were compared with regard to their capacity to metabolize structurally different promutagens. The sensitivities of both activation systems were evaluated by comparing the induction of SCE in H4IIEC3/G- cells themselves with that ih V79 cells co-cultured with hpc. Of the six chemicals tested, aflatoxin B1 (AFB1), cyclophosphamide, dimethylnitrosamine and nitrosomorpholine (NM) were shown to be inducers of SCE in H4IIEC3/G- cells as well as in V79 cells with hepatocyte activation. 7,12-Dimethylbenzanthracene gave positive responses in hpc/V79 co-cultures but not in H4IIEC3/G- cells whereas benzo[a]pyrene was negative in both systems. These results suggest that H4IIEC3/G- cells retain metabolic activities to convert different indirect mutagens into their active forms and clearly indicate the presence of liver specific cytochrome P-450-dependent mono-oxygenases. However, freshly isolated hepatocytes are more efficient in metabolizing the test compounds. Although hpc provide only external activation, the V79 cells system appears to be more sensitive for the detection of promutagens.

Animals↗

Pancreatic transplantation: scintigraphy, US, and CT.

Twenty-one patients with insulin-dependent diabetes mellitus received simultaneous renal and segmental pancreatic transplants. A retrospective analysis of 112 real-time ultrasound (US) images, 108 technetium-99m glucoheptonate scinti-scans, 55 computed tomography (CT) scans, and 11 cystograms was performed. Complications that were observed included pancreatic transplant rejection, pancreatitis, arteriovenous occlusions, hemorrhage, abscesses, and extravasation at the pancreaticocystostomy site. Scintigraphy is a sensitive indicator of normal transplant function but is non-specific when findings are abnormal. Real-time US aids in the differentiation of acute rejection from pancreatitis and arteriovenous occlusion. CT is helpful for evaluation of postoperative complications. Imaging may play an important role in the noninvasive management of pancreatic transplants.

Adult↗

Immunotherapy of murine sarcomas with auto-anti-idiotypic monoclonal antibodies which bind to tumor-specific T cells.

Hybridomas producing monoclonal antibodies (mAb) were obtained from BALB/c mice immunized against either of two transplanted, chemically induced syngeneic sarcomas, MCA-1490 or MCA-1511. Two mAb, 4.72 and 5.96, were obtained, one from each immunization. They were found to have apparent anti-idiotypic specificity in that they, when injected s.c., primed naive BALB/c mice for delayed-type hypersensitivity that was specific for the immunizing tumor and required homology at genes linked to the Igh-1 allotype locus. Neither mAb bound tumor antigen. When mice with established transplants of MCA-1490 or MCA-1511 were treated by repeated i.p. injections of the appropriate anti-idiotypic mAb (4.72 and 5.96, respectively), a significant reduction in tumor growth was observed in those mice that had received the appropriate mAb. The idiotope defined by mAb 4.72 was expressed by T cells in mice responding to MCA-1490. mAb 4.72 bound to T cell suppressor factors that were specific for MCA-1490 and were derived from T cell hybridomas or sera of mice bearing MCA-1490. mAb 4.72 also bound to cells from lymph nodes draining the area of a growing MCA-1490 tumor. It was used, in combination with cell sorting, to establish a T cell line, which mediated delayed-type hypersensitivity to MCA-1490 and inhibited the outgrowth of MCA-1490 in BALB/c mice. Thus, mAb specific for idiotopes on T cells responding to syngeneic tumor antigen had both direct immunotherapeutic activity and could be used to establish cultures of tumor-reactive T cells.

Animals↗

Bicycling performance in Gambian children: effects of supplements of riboflavin or ascorbic acid.

Sixty rural Gambian children between 10 and 14 years of age with normal haematological status but generally poor riboflavin status and some evidence of poor ascorbic acid status were recruited for study at the beginning of the rainy season. Children were allocated to three treatment groups to receive, twice weekly, either a placebo or a supplement of riboflavin or ascorbic acid. Before receiving the supplement, and on two subsequent occasions 6 weeks apart children performed an exercise regimen on a bicycle ergometer during which expired air was collected, heart rate monitored and lactate accumulation measured. A modest but significant improvement in ascorbic acid status occurred in response to supplement and the riboflavin supplement enhanced the overall improvement in riboflavin status observed. There was no measurable change in bicycling performance during the study period in any of the treatment groups.

Adolescent↗

Homozygosity for a new type of G gamma (A gamma delta beta)zero-thalassemia in a Malaysian male.

Hematological and clinical data are presented for a young Malay patient with a homozygous (delta beta)zero-thalassemic condition. His red blood cells contained 100% fetal hemoglobin with alpha and G gamma chains only. Detailed gene mapping defined a large deletion with a 5' end between the Aha III and Apa I sites, some 200-400 bp 5' to the A gamma globin gene and a 3' end beyond sequences 17-18 kb 3' to the beta globin gene. This G gamma (A gamma delta beta)zero-type of thalassemia is different from all the other six types described before. Comparison of the hematological data of this patient with those of homozygotes for either the Sicilian or Spanish types of G gamma A gamma (delta beta)zero-thalassemia showed no differences; all homozygotes have a moderate anemia which is accentuated by the relatively high oxygen affinity of the Hb F containing erythrocytes.

Child↗

Magnetic resonance imaging of the lumbar spine. A comparison with computed tomography and myelography.

Two hundred and fifty patients were referred for magnetic resonance imaging (MRI) of the lumbar spine. Computed tomography (CT) and MRI were performed in 50 patients and MRI, CT and myelography in 20 patients. Twenty patients had surgical confirmation of the imaging studies. MRI was best for demonstrating degenerated discs. MRI was better than CT for demonstrating disc bulge without herniation, and MRI was slightly better for herniated disc demonstration than CT. Myelography did not demonstrate degenerated discs.

Humans↗

[The delay of a time-limitation for thawed blood. New perspectives].

In order to comply with the needs for delayed transfusion in current practice (rare blood types dispatched to other centers, thawed blood not finally transfused to a patient, blood bank supply of Rh negative blood), we have investigated preservative media for thawed blood. We have previously shown that thawed RBC concentrates resuspended in isologous or autologous plasma remain viable and functional for 72 hours. We have extended these investigations by resuspending thawed RBC concentrates in an original synthetic preservative medium designed in our laboratory, containing: (table; see text) The following parameters have been investigated before freezing and during 15 days following thawing and washing: sterility, pH and 2,3-DPG, ATP and energy charge, free Hb levels in the supernatant, 24 h post-transfusion life and half-life of 51Cr-labeled RBC. This preservative allows the conservation of thawed RBC for up to nine days at +4 degrees C. During that time, sterility is maintained, pH is 6.80, 2,-3-DPG levels are 50% of the original values, ATP levels are 100% of the original values, free Hb is 122 mg per blood unit, energy charge is 0.90; RBC labeled 7 days after thawing showed a 89% survival rate 24 h after transfusion and a half-life of 19 days.

2,3-Diphosphoglycerate↗

Malays with thalassaemia in West Malaysia.

Hereditary haemolytic anaemias have been found to be a significant cause of haemolytic disease in West Malaysia. This paper reports a micromapping study of 916 healthy Malay males from June to August 1983 to determine the distribution of the relevant thalassaemia genes in West Malaysia. Beta thalassaemia trait was found in 2.18%, HbE 3.49% and alpha thal2 (alpha+) trait in 26%. Of the sixteen transfusion dependant Malay thalassaemic patients at the Paediatric Unit, National University of Malaysia, eight patients had HbE beta thalassaemia and the rest are beta thalassaemia major; these patients who are transfusion dependant receive inadequate treatment. Prevention is the only resort.

Adolescent↗

Stimulation of poly(ADP-ribosyl)ation during Ehrlich ascites tumor cell "starvation" and suppression of concomitant DNA fragmentation by benzamide.

Incubation of Ehrlich ascites tumor cells in their own ascites fluid induced a reversible metabolic adaptation to these "starvation" conditions which was associated with a fragmentation of DNA. Endogenous poly(ADP-ribose) residues also increased, reaching within 1-3 h values 6-10 times higher than in cells taken directly from the mouse peritoneum. The NAD content changed only slightly while dimethyl sulfate-induced accumulation of poly(ADP-ribose) (10-fold within 30 min) was associated with a rapid depletion of NAD (85% lost at 30 min). Nevertheless, turnover of poly(ADP-ribose) as measured by the decay rate of the polymer upon addition of benzamide was dramatically stimulated in both situations, reaching apparently identical half-lives (t 1/2 approximately equal to 1 min) in "starved" and in alkylated cells. However, since penetration of benzamide into the nucleus may be the rate-limiting factor in these studies, turnover of poly(ADP-ribose) in dimethyl sulfate-treated cells may still be much higher than that in "starved" cells. In cells treated with dimethyl sulfate, suppression of poly(ADP-ribose) synthesis by benzamide did not interfere with DNA fragmentation or with DNA resealing as determined by the nucleoid procedure. By contrast, starvation induced a type of DNA incision that was prevented by benzamide. It is proposed that starvation-induced scission of DNA occurs at specific ("regulatory?") sites requiring poly(ADP-ribose) formation to take place, while fragmentation of DNA at random as seen with alkylating agents is associated with, but not dependent on, increased poly(ADP-ribosyl)ation.

Animals↗

DNA fragmentation and NAD depletion. Their relation to the turnover of endogenous mono(ADP-ribosyl) and poly(ADP-ribosyl) proteins.

Treatment of Ehrlich ascites tumor cells with the trifunctional alkylating agent 2,3-5-tris(ethyleneimino)benzoquinone-1,4 (triaziquonum) led to rapid fragmentation of DNA and depletion of NAD while poly(ADP-ribose) synthetase activity showed a retarded increase. Poly(ADP-ribosyl) residues in treated cells increased 4- to 30-fold, but transiently, and in a dose-dependent manner, exhibiting the same initial kinetics as the loss of NAD and the appearance of DNA strand breaks when determined by the nucleoid method. Although the amounts of "activated ADP-ribosyl" groups present in the substrate NAD (80 nmol/10(8) cells) exceeded by far basal and triaziquonum-induced poly(ADP-ribosyl) groups (up to 250 pmol/10(8) cells), accelerated formation of the polymer, nevertheless, may explain at least partially the loss of NAD seen under these conditions. Addition of benzamide, a potent inhibitor of poly(ADP-ribose) synthetase, to triaziquonum-treated cells effected an immediate drop of poly(ADP-ribose) to basal values. The data indicate a biphasic decay, the half-life of greater than 85% of the polymeric ADP-ribosyl groups exhibiting a t1/2 less than 1 min under these conditions, while the residual fraction died away with t1/2 approximately 6 min. Treatment with the DNA fragmenting agent also led to a 9-fold increase of nuclear mono(ADP-ribosyl) groups, while cytoplasmic mono(ADP-ribosyl) protein conjugates were not significantly affected. The apparent half-life of nuclear mono (ADP-ribosyl) protein conjugates (8-10 min) at peak elevation was definitely longer than that of poly(ADP-ribosyl) residues. This result is consistent with the interpretation that accumulation of mono(ADP-ribosyl) groups is due to a retarded removal of the primary ADP-ribosyl group from the acceptor protein by a separate mono(ADP-ribosyl) protein glycohydrolase, being the rate-limiting step in the overall turnover of poly(ADP-ribosyl) residues.

ADP Ribose Transferases↗

Production of T-cell lines with inhibitory or stimulatory activity against syngeneic tumors in vivo. A preliminary report.

We obtained Thy-I-positive cells directly from growing methylcholanthrene-induced (MCA-1510) sarcomas using fluorescence-activated cell sorting, then cultured these lymphocytes in medium containing Interleukin-2 and tested their activity in vivo against various MCA-sarcoma lines with the Winn assay. We found that cultured T cells from small MCA-1510 tumors (17 days after transplantation) significantly inhibited the growth of that particular sarcoma, but not of three other MCA-tumor lines tested, while cultured T cells from large MCA-1510 sarcomas (41 days after transplantation) significantly enhanced the growth of that tumor, but not of an unrelated tumor, MCA-1460. The former cells were primarily Lyt-1+, 2+ while the latter were primarily Lyt-1+, 2+.

Animals↗