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Biomedical subjects

G Jacob

Publications and source records attributed to G Jacob.

At least 73 records · Page 4Linked to original sources
PubMed1991

Factors influencing the establishment of tumour-infiltrating lymphocyte cultures from human breast carcinoma and colon carcinoma tissue.

Tumour-infiltrating lymphocytes (TIL) were obtained from breast and colon tumour tissue and cultured in vitro in the presence of recombinant human interleukin-2. Seven of 35 breast tumours and five of 41 colon TIL cultures were established in vitro: proliferation rates of greater than 10(3) were achieved. The cytotoxic capacity of these cells was determined against the cell lines K562 and SW742, and percentage cytotoxicity levels of greater than 97% and 79%, respectively, were seen. An inverse relationship between the ability of TIL to kill and their proliferative capacity was observed in all cultures. The prominent phenotype was CD3 positive, with greater than 55% of TIL expressing this antigen; there was no expression of CD16. The expression of CD56 and CD25 varied, being maximumly expressed on 64% and 38% of TIL, respectively. When greater than 90% of TIL expressed CD3, the ability of the culture to kill the target cell lines was low; only when there was an increase in the proportion of cells expressing CD56 and a decrease in the expression of CD3 was there high cytotoxicity. This study indicates that the TIL which proliferate in vitro in the presence of interleukin-2 are not necessarily the mediators of cytotoxicity.

Adult↗
PubMed1991

The hydrolysis of phosphatidylinositol 4-phosphate in membranes of Xenopus laevis oocytes: characteristics of a phosphomonoesterase.

1. Phosphatidylinositol 4-phosphate (PtdIns4P) is degraded by isolated membranes from Xenopus laevis oocytes. 2. Incubation of [4-32P]PtdIns4P with membranes yields only radioactive inorganic phosphate, indicating the presence of a phosphomonoesterase. 3. Membranes hydrolyze Ptd[2-3H]Ins4P to produce mainly Ptd[2-3H]Ins in the lipid phase. In this incubation [3H]inositol and inositol monophosphate appear in the water phase. 4. Membrane incubations of Ptd[2-3H]Ins4P carried out in the presence of excess non-radioactive Ins(1,4)P2 allows the trapping of small amounts of [3H]Ins(1,4)P2. These results demonstrate the presence of a phospholipase C. 5. Testing several phosphorylated analogs, it is determined that fructose 1,6-bisphosphate and alpha-glycerophosphate are potent inhibitors of the oocyte PtdIns4P phosphomonoesterase.

Animals↗
PubMed1991

Natural killer cell activity following cryosurgery of normal and tumour bearing liver in an animal model.

Cryosurgery is a useful tool to treat unresectable liver carcinoma. In addition to the local effects of freezing, cryosurgery is thought to affect host immune response. We tested this by measuring natural killer (NK) cell cytotoxicity following cryosurgery of normal liver and an implanted liver tumour in the rat. Controls underwent sham cryosurgery. NK cytotoxicity was enhanced following cryosurgery of normal liver and liver tumour.

Animals↗
PubMed1991

Cardiovascular responses to serotonin in experimental liver disease.

Recent evidence suggests that serotonergic mechanisms within the cardiovascular system are activated and may be important in the development of the hyperkinetic circulation and the maintenance of portal hypertension in cirrhotic patients. The in vivo pressor and positive chronotropic response together with the in vitro contractile responses of aortic rings and portal veins to serotonin were studied in three different rat models of cirrhosis, portal hypertension and jaundice: the portal vein-ligated rat, the carbon tetrachloride-induced cirrhotic rat, the chronic bile duct-ligated cirrhotic rat and the 3-day noncirrhotic, nonportal hypertensive-jaundiced rat. In addition, the activity of the enzyme monoamine oxidase type A was determined in lung homogenates prepared from the four groups of sham and treated animals. In the four different groups of sham-treated or operated pithed rats, serotonin caused a dose-dependent increase in mean arterial blood pressure without any effect on the heart rate. The pressor responses to serotonin in the three models of portal hypertension were significantly attenuated from their respective sham group. In the 3-day noncirrhotic, nonportal hypertensive-jaundiced rats, the pressor response was no different than that seen in the sham-operated rats. No evidence of consistent potentiated or blunted in vitro reactivity to serotonin of arterial rings and portal veins from the four groups of rats was seen. Portal hypertension, cirrhosis and hyperbilirubinemia had no effect on the activity of monoamine oxidase type A. These data demonstrate that portal hypertension is associated with an attenuated pressor response to serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

In vitro vascular responsiveness to norepinephrine in experimental portal hypertension.

It has been postulated that loss of response to norepinephrine accounts in part for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease. The in vitro vascular responsiveness to norepinephrine was measured in aortic rings and portal veins excised from four different rat models of hepatic disease with and without portal hypertension, hepatocellular damage, and hyperbilirubinemia--the carbon tetrachloride (CCl4) cirrhotic rat with portal hypertension, the five-week chronic bile duct ligated and resected (CBDL) cirrhotic rat with portal hypertension and hyperbilirubinemia, the 10-day partial ligated portal vein (PVL) portal hypertensive rat without hepatocellular damage and hyperbilirubinemia, and the three-day bile duct ligated (ABDL) rat with acute hepatocellular damage and hyperbilirubinemia but without portal hypertension. Sham-treated or operated groups for each model were also prepared. Vascular reactivity of the aortic rings to norepinephrine was potentiated in the three portal hypertensive groups, and attenuated in the model of acute cholestasis. No consistent pattern of response to norepinephrine was evident in the portal veins. Based upon the presented in vitro data and the discussed limitations of an in vitro study, we conclude that it is unlikely that the loss of response to norepinephrine accounts for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease.

Animals↗
PubMed1990

Chromosome studies in eleven colorectal tumors.

Cytogenetic analysis is presented on seven freshly derived colorectal tumors and four established cell lines (SW 742, SW 480, SW 948, and HT 29). No chromosome change was common to all tumors, although previous nonrandom findings were confirmed. Single chromosome abnormalities were identified in two cases, 47,XX,+i(7p) and 46,XX,-17,+der(17),t(17;?)(p;?), and their relevance to tumor origin and development is discussed. The association of i(8q) with tumors of the rectosigmoidal region is confirmed, and it is suggested that other rearrangements involving loss of 8p may have the same association. Abnormalities resulting in loss of 20p and duplication of 20q, not previously reported as a nonrandom change, were seen in seven out of 11 cases.

Adenocarcinoma↗
PubMed1988

Comparison of excision versus cryosurgery of an HSV-2-induced fibrosarcoma. I. Survival, extent of metastatic disease and host immunocompetence following surgery.

Cryosurgery and excision were used to treat primary tumours of HSV-2-transformed hamster tumour sublines, and post-operative survival and the extent of metastatic disease were compared in the two groups. An inferior prognosis was observed following cryosurgery although the extent of metastatic disease was similar in both groups. Using this model it would appear that cryosurgery enhances the development of micrometastases rather than affecting the number of cells shed from the primary tumour during surgery. To investigate the underlying causes of the decrease in survival following cryosurgery, in vitro assays were used to monitor host immunocompetence following surgery. The results showed that whilst natural killer cell cytotoxicity was only marginally depressed, mitogen responsiveness and lymphocyte participation in a mixed lymphocyte reaction were severely reduced 3-7 days post-cryosurgery. In parallel with immunosuppression, extensive cell proliferation in the spleen of cryosurgically treated tumour-bearing animals was observed. Histological examination of the spleen demonstrated the presence of large numbers of transformed cells which correlated with the loss of mitogen responsiveness and the ability to participate in a mixed lymphocyte reaction. Further studies (manuscript submitted for publication) have demonstrated that spleen cells from animals whose tumour is treated by cryosurgery are capable of suppressing immunocompetence in vitro, implying they have a role in the uncontrolled growth of micrometastases in vivo.

Animals↗
PubMed1988

Characterisation of suppressor cells generated following cryosurgery of an HSV-2-induced fibrosarcoma.

Cryosurgery of a primary HSV-2-induced hamster fibrosarcoma resulted in the generation of a population of suppressor cells. These cells were detectable in the spleen 1-10 days post-cryosurgery by their ability to suppress the proliferation of immunocompetent splenic T-lymphocytes following exposure to concanavalin A (Con A). The spleens of tumour-bearing (t.b.) animals which received cryosurgery 3 days previously displayed gross splenomegaly due to the generation of large numbers of highly proliferative erythroblasts. The erythroblast cells were unlikely to be the source of suppression since time course studies have demonstrated the presence of suppressor cells before and after their appearance in the spleen. The erythroblasts therefore probably reflected a response by the host to regenerate the erythrocytes lost during surgery and their presence was independent of the appearance of suppressor cells. Characterisation of the suppressor cell has revealed it to be non-adherent and esterase negative making it unlikely to be of macrophage (MO) lineage. This was confirmed by the ability of splenic MOs from day 3 t.b. cryosurgery-treated animals to completely restore Con A-dependent T-lymphocyte proliferation following MO depletion. As nylonwool column-eluted cells are able to suppress Con A-dependent T-lymphocyte proliferation, it seemed unlikely that B-lymphocytes play a role in cryosurgery-induced immunosuppression. These findings suggest that cryosurgery of a t.b. animal results in the generation of a population of T-lymphocytes capable of suppressing Con A-dependent T-lymphocyte proliferation, and infers that these cells contribute to the inferior prognosis following cryosurgery as compared to excision of a metastatic tumour.

Animals↗
PubMed1988

Loss of polymorphic A and B locus HLA antigens in colon carcinoma.

In the present study we have confirmed that approximately one third of human colorectal carcinomas fail to express the HLA - A,B,C monomorphic determinant reactive with the W6/32 MAb, and 44% express class II HLA antigens as shown by reactivity with NFK-1 MAb. Reduced staining with the W6/32 MAb was not always associated with the loss of beta 2m. In addition, the expression of HLA-A2 and Bw4 class I specific haplotypes on normal colon epithelium and tumour biopsy tissue was assessed. All normal colonic epithelia stained positively with MAb against A2 and Bw4 antigens, but a loss of these determinants was shown on tumour biopsies from patients tissue typed for the respective specificities. Loss of the A2 haplotype was shown in 4 of 15 tumour tissue samples, and loss of Bw4 specificities in 5 out of 7 tissue samples. The failure to detect specific loci determinants was not necessarily associated with loss of reactivity with W6/32 MAb.

Adenocarcinoma↗
PubMed1988

Polylysine and polyamine stimulation of the phosphatidylinositol kinases of amphibian oocyte membranes.

Phosphatidylinositol kinase present in Xenopus laevis oocyte membranes catalyzes the formation of phosphatidylinositol 4-phosphate using phosphatidylinositol and ATP as substrates while the activity of a second enzyme, phosphatidylinositol-4-phosphate kinase, results in the synthesis of phosphatidylinositol 4,5-bisphosphate. Large (Mr greater than 20,000) homopolymers of L-lysine or L-ornithine can stimulate the activity of both of these enzymes by at least 2-fold at 10-20 microM concentrations. Under similar conditions poly-L-arginine fails to stimulate the reaction causing a partial inhibition. Smaller polylysine (25 lysines) or lysine-rich oligopeptides such as one corresponding to the last 14 amino acids of the carboxyl end of c-Ki-ras 2 protein produce appreciable stimulation of phosphatidylinositol but at concentrations of 300-500 microM. Spermine and spermidine at millimolar concentrations also stimulate exogenous phosphatidylinositol phosphorylation. The amino-glycoside antibiotic neomycin has a biphasic effect, stimulating the phosphatidylinositol kinase at concentrations below 0.5 mM and strongly inhibiting at higher concentrations. Polylysine also moderately stimulates the loss of radioactivity of phosphatidylinositol-4-[32P] phosphate observed in oocyte membranes. Polylysine and polyornithine do not change the apparent Km for ATP of the phosphatidylinositol kinase but increase the Vmax of the reaction.

1-Phosphatidylinositol 4-Kinase↗
PubMed1988

Proteolysis of mitochondrial-coded and nuclear-coded proteins found in yeast mitochondria.

The rate of degradation of radioactive labeled mitochondrial proteins synthesized both in vitro and in vivo by isolated yeast mitochondria and growing yeast cells respectively, has been studied. It was found that the in vitro-synthesized mitochondrial proteins are rapidly degraded by an energy-dependent proteolytic system. Under the same experimental conditions the in vivo-synthesized mitochondrial proteins are slowly degraded to a limited extent by a protease which is slightly inhibited by ATP. During this period, the mitochondria are coupled and metabolically active. It is proposed that mitochondria possess an energy-dependent proteolytic system that recognizes as substrates either "abnormal" proteins or unassembled protein subunits encoded in the mitochondrial genome. An apparently different system, which is independent of energy, seems to be responsible for the slow and limited degradation of "normal" mitochondrial proteins.

Adenosine Triphosphatases↗
PubMed1987

Male choriocarcinoma of the spleen: a case report.

The success with treatment of extragonadal germ cell tumours is well recognized and emphasizes the need for an early diagnosis. In young men presenting with undifferentiated carcinoma a non-testicular germ cell tumour should be considered. We report a case of choriocarcinoma involving the spleen.

Adult↗
PubMed1986

Minimum effective dose of etodolac for the treatment of rheumatoid arthritis.

Etodolac was compared with aspirin and placebo for efficacy and safety, and a minimum effective dose was established in 264 patients with adult-onset, active rheumatoid arthritis. In this six-week, 14-center, double-blind, parallel-group investigation, preceded by a washout period of up to two weeks, patients received daily doses of etodolac at 50, 100, or 200 mg/d; aspirin at 3,900 mg/d; or placebo. Both etodolac at the highest dose and aspirin produced statistically significant improvement from baseline in all disease activity assessments measured at four- and six-week end points and were superior to placebo in the majority of assessments. A greater number of patient complaints occurred with aspirin, especially in regard to gastrointestinal-related and otologic side effects. A significant therapeutic dose response was evident among the etodolac groups without an increase in side effects. Although the 100-mg/d dose was effective in many of the efficacy parameters measured, the 200-mg/d dose, which is comparably efficacious to aspirin 3.9 g/d, was suggested as the minimum effective dose for the relief of the signs and symptoms of active rheumatoid arthritis.

Acetates↗
PubMed1985

Effect of ethionine on the in vitro synthesis and degradation of mitochondrial translation products in yeast.

The effect of ethionine, an amino acid analog of methionine, has been studied in Saccharomyces cerevisiae in relation to cell growth, oxygen consumption, in vitro protein synthesis of mitochondrial translation products (MTPs) and the degradation of those mitoribosomally made proteins by an ATP-dependent process present within the organelle. Ethionine was found to increase the generation time of those cells already committed to cell division and to abolish the initiation of new cell cycles. Oxygen consumption of cultures grown in the presence of the analog was drastically reduced. Ethionine was also found to impair the incorporation of methionine and leucine into mitochondrial translation products, however the synthesis of proteins was not totally blocked and, apparently, mitochondria utilized ethionine as a precursor amino acid. MTPs synthesized by isolated mitochondria in the presence of ethionine were rapidly degraded inside the organelle at a faster rate compared with the normal proteins synthesized under identical conditions in the mitochondria. It is also shown that these in vitro synthesized proteins are degraded by an ATP-stimulated proteolytic system, as has been previously established.

Adenosine Triphosphate↗
PubMed1985

An assessment of tumor cell viability after in vitro freezing.

The identification of the minimum lethal temperature for tumor cells in vivo is difficult because of the secondary factors that are associated with the cryoinjury. This study attempts to identify this temperature by a combination of in vitro and in vivo techniques. Suspensions of Walker carcinoma cells were frozen at a rate of 1 degree C/min without cryoprotection, to either -10, -15, -20, -25, -30, -35 or -40 degrees C and held at that temperature for either 0, 10, 20, or 30 min. After spontaneous rewarming viability was assessed by a combination of vital dye studies and the growth of tumor cells inoculated into the liver and subcutaneous tissue of male, Sprague-Dawley rats. Trypan blue studies indicated that less than 1% of the cells frozen to -35 degrees C were considered viable, yet significant tumor take rates were noted, suggesting that for some cells the cryoinjury is reversible. As expected tumor take rates were reduced by lowering the temperature but were independent of the holding time. The volume doubling time and final tumor volume of the subcutaneous tumors was similar to that of controls, indicating that the growth potential of the cells which survive freezing is normal. The minimum lethal temperature was dependent upon the site of inoculation, subcutaneous tumors developing from cells frozen to -35 degrees C, whereas liver tumors did not develop from cells frozen beyond -25 degrees C, this may have important clinical implications.

Animals↗