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Biomedical subjects

E Jacobs

Publications and source records attributed to E Jacobs.

At least 145 records · Page 8Linked to original sources
PubMed1986

Psychiatric sequelae following surgical treatment of breast cancer.

Breast cancer has been the most carefully studied site of tumor from a psychological point of view. A range of interventions have been developed to assist the woman and her family in the emotional adjustment to breast cancer and its treatment. Many of these have been developed 'by women for women' and by their insistence that the medical community give more attention to this aspect of medical care. Rehabilitation now centers far more on breast reconstruction then previously. The psychologic understanding of problems posed by breast cancer has been used to develop rational and appropriate psychosocial interventions to reduce emotional distress. This model for development of support in breast cancer should be applied to psychologic management of patients with cancers of other sites, particularly those that carry high emotional distress and that place extensive demand on an individual's adaptive capacities.

Adaptation, Psychological↗
PubMed1985

Antitumor properties of vindesine-monoclonal antibody conjugates.

The anticancer alkaloid vindesine (VDS) was conjugated to four mouse monoclonal antibodies recognizing human tumor-associated antigens. The antibodies were 96.5 (antimelanoma, IgG2a); 791T/36 (antiosteogenic sarcoma, IgG2b); 11.285.14, and 14.95.55 (anticarcinoembryonic antigen, IgG1 and IgG2a respectively). Conjugates VDS-96.5 and VDS-791T/36 were tested in vitro and shown to be specifically cytotoxic for target cells expressing the appropriate antigen. The in vivo effects of the antibodies and conjugates were tested against human tumor xenografts in athymic or immunodeprived mice using multiple treatments. Conjugate VDS-96.5 retarded the initial growth of a melanoma xenograft, whereas free antibody was without effect. Similarly, VDS-791T/36 but not free antibody retarded the growth of osteogenic sarcoma 791T. The most marked antitumor effects observed were those obtained with VDS conjugates of the anti-CEA antibodies against a colorectal tumor xenograft. Antibody 14.95.55 suppressed tumor growth both alone and as a VDS conjugate, whereas 11.285.14 produced only a slight effect alone but an almost complete and lasting suppression of tumor growth as a VDS conjugate. Free VDS had little effect at nontoxic levels. Acute studies showed that VDS-11.285.14 conjugate was considerably less toxic than free VDS in Balb/c mice.

Animals↗
PubMed1985

Regulation of ureaamidolyase synthesis in Saccharomyces cerevisiae, RNA analysis, and cloning of the positive regulatory gene DURM.

In S. cerevisiae, the synthesis of ureaamidolyase is subject to at least two different forms of regulation: nitrogen catabolite repression and induction by allophanate. Two positive regulatory genes DURM and DURL are involved in the induction process. We have measured the levels of mRNA homologous to the DUR2,1 gene in conditions of ureaamidolyase induction and in regulatory mutants. The amounts of DUR2,1 enzyme and messengers are well coordinated; moreover, the half life of DUR2,1 messengers is identical in the presence or absence of inducer. These data suggest that the ureaamidolyase production is probably controlled at the level of transcription. From a pool of hybrid plasmids carrying Sau3A fragments representing the entire yeast genome, a 13 kb DNA fragment containing the regulatory gene DURM was cloned by complementation of a durM mutation which prevents the growth on allantoin as sole nitrogen source. Cells containing the cloned DNA recover the inducibility of ureaamidolyase by allophanate. Four RNA transcripts have homology to this 13 kb DNA fragment but the study of subcloned restriction endonuclease fragments allowed us to map the DURM regulatory gene within a 4 kilobase pair region. This fragment encodes a 1 kb transcript. The level of this RNA is the same in induced and non-induced cells.

Carbon-Nitrogen Ligases↗
PubMed1985

Adherence inhibition assay: a specific serological test for detection of antibodies to Mycoplasma pneumoniae.

Antibodies directed against the adherence-mediating protein of Mycoplasma pneumoniae were measured by an adherence inhibition assay. Pretreatment with antibody-containing sera reduced the attachment of sheep erythrocytes to Mycoplasma pneumoniae layers grown in flat-bottom microtiter plates. The degree of attachment of erythrocytes was estimated by lysis with distilled water and measurement of absorbance in a microtiter reader. Sera tested included 126 sera from patients with suspected Mycoplasma pneumoniae respiratory infection and 60 sera from patients with serologically confirmed respiratory infection of other origin. Examination of human sera by both complement fixation using glycolipid as antigen, and the adherence inhibition assay indicated a high degree of specificity of the latter. Furthermore, titer increases parallel to complement fixation titers were found in six paired sera, and testing of separated IgM showed high reactivity in this immunoglobulin fraction. The adherence inhibition assay is a reproducible method which is relatively easy to perform. It may be of importance especially when a non-specific complement fixation reaction due to cross-reaction is suspected.

Animals↗
PubMed1985

Natural killer cell activity in childhood acute lymphoblastic leukaemia in remission.

Fifteen children with acute lymphoblastic leukaemia (ALL) in remission receiving maintenance chemotherapy and 12 ALL patients off treatment and in remission were tested for natural killer (NK) cell activity in vitro. Compared with a control population the children with ALL receiving maintenance chemotherapy had low levels of NK cell activity. This effect was not due to a specific reduction in NK cell numbers since proportions of mononuclear cells detected by the monoclonal antibodies HNK-1 (Leu-7) and Leu-11a were normal. Furthermore NK cell activity in patients could only be partially increased by pre-incubation of effector cells with interferon (alpha IFN). These studies confirm the lack of NK cell activity in children with ALL and show that this phenomenon is directly related to functional NK cell impairment. Our study has further shown that this effect is transient since ALL patients off treatment and in remission showed normal levels and augmentation of NK cell activity.

Acute Disease↗
PubMed1985

Studies on the mechanism of action of an antibody-targetted drug-carrier conjugate.

A conjugate of methotrexate-substituted human serum albumin (HSA) coupled to a monoclonal antibody (791T/36) recognizing osteogenic sarcoma cell lines has been reported previously to have good cytotoxicity and specificity in vitro (Garnett et al., 1983). Cytotoxicity was assessed by the median inhibition (IC50) of [75Se]selenomethionine uptake resulting from a 24-h incubation of conjugate with antigen-bearing 788T or 791T osteogenic sarcoma cell lines. In the present work, the properties of this conjugate have been investigated to determine whether cytotoxicity is optimal with respect to binding activity, and aspects of the mechanism of action investigated by the effects of specific inhibitors of biochemical processes on conjugate cytotoxicity. Conjugate cytotoxicity was reduced by ammonium chloride suggesting that endocytosis and an acidic internal compartment were involved in the mechanism of action. The specific inhibitors of proteinases leupeptin and E64 also reduced conjugate cytotoxicity, while the inhibitors pepstatin A and chymostatin had no effect, demonstrating that cysteine proteinases were involved. The inhibitor of methotrexate transport, folinic acid, reduced the cytotoxicity of conjugate more than that of free methotrexate whereas folic acid had no effect on either, indicating that the methotrexate transport system may still be involved but in a different manner to the free drug. The cytotoxicity of these conjugates is probably near optimal for maximum selectivity.

Antibodies, Monoclonal↗
PubMed1984

Antigenicity and drug susceptibility of human osteogenic sarcoma cells "escaping" a cytotoxic methotrexate-albumin-monoclonal antibody conjugate.

Cells of osteogenic sarcoma line 791T were treated in vitro with a selectively cytotoxic methotrexate-human serum albumin-monoclonal antibody conjugate at concentrations which were toxic but allowed the "escape" of a small number of tumour cell colonies (less than 0.3% compared with controls). These colonies were propagated as clones in order to test their expression of the monoclonal antibody ( 791T /36)-defined antigen and their resistance to methotrexate (MTX) by comparison with parental cells. Most of the conjugate-treated clones were incapable of prolonged growth and died out, in contrast to untreated 791T clones which virtually always grow progressively. Only four treated clones grew at rates comparable with the parental line. Flow cytofluorometric analysis indicated that the surviving clones expressed normal or enhanced amounts of 791T /36-defined antigen and clonogenic assays demonstrated that they were sensitive to cytotoxicity by MTX. As could be predicted from these results, further exposure to the conjugate inhibited growth of the clones at doses comparable with those active against parental 791T cells. It is concluded that tumour cell clones emerging after exposure to a toxic concentration of a drug-antibody conjugate are not necessarily modified resistant clones, but may have severely impaired long-term growth potential or be susceptible to further contact with the same conjugate.

Antibodies, Monoclonal↗
PubMed1984

Psychosocial issues in breast reconstruction. Intrapsychic, interpersonal, and practical concerns.

Because the decision to have or not to have breast reconstruction is multiply determined, in-depth inquiry should be made into the patient's intrapsychic (self-directed) motives and interpersonal factors that contribute to her choice. This article discusses five major variables that enter into the final decision. These include knowledge of the procedure, economic resources, medical conditions, psychological dynamics, and reactions of significant others in the patient's life, including spouse, physicians, and mother.

Body Image↗
PubMed1983

Preparation and properties of a drug-carrier-antibody conjugate showing selective antibody-directed cytotoxicity in vitro.

The preparation and properties of a drug-carrier-antibody preparation are reported. The antifolate chemotherapeutic agent methotrexate was covalently coupled to human serum albumin as a carrier. The carrier-drug preparation was then chemically linked to a monoclonal antibody, raised originally against a human osteogenic sarcoma cell line, 791T, in a manner permitting retention of antibody-binding activity. The cytotoxic properties of the conjugate were tested in vitro in comparison with carrier-methotrexate and free methotrexate against a panel of tumour cell lines containing both antigenically cross-reactive cell lines and cell lines having low antigenic cross-reactivity with the monoclonal antibody. The cytotoxicity tests demonstrated that coupling of methotrexate to carrier caused a loss of some drug activity but that coupling of the antibody to the carrier-drug preparation permitted full expression of drug cytotoxicity against antibody-reactive cell lines. It was further demonstrated that the conjugate was selective in its action and was preferentially cytotoxic towards antibody-reactive cell types. The cytotoxicity against antibody-reactive cell lines was shown by competitive inhibition by free antibody to be entirely dependent on antibody binding. A clonogenic assay showed that the conjugate was capable of killing greater than 99% of 791T target cells. These results indicate that a drug-carrier antibody conjugate can be synthesized which has all the in vitro properties theoretically necessary for a successful antibody-targeted cytotoxic agent.

Animals↗
PubMed1983

Selective cytotoxicity against human tumour cells by a vindesine-monoclonal antibody conjugate.

The anti-mitotic drug vindesine was coupled chemically to a monoclonal antibody raised originally against the human osteogenic sarcoma cell line, 791T. The cytotoxicity of the conjugate in vitro was tested, in comparison with free vindesine, against sarcoma 791T and other antigenically cross-reactive osteogenic sarcoma-cell lines, and also against tumour cell lines which have no detectable reaction with the monoclonal antibody. Continuous exposure of cultured 791T cells indicated that the vindesine was partially inactivated following conjugation since the conjugate was less toxic than the free drug. However, antibody-binding activity was essentially preserved following conjugation. Despite diminished drug activity in the conjugate, assays designed to mimic antibody binding to tumour in which target cells were treated with conjugate and washed before culture, showed selective cytotoxicity for osteogenic sarcoma lines with little or no effect on non-cross reactive control cells. In comparison, free vindesine was toxic equally for all cell lines and free antibody was non-toxic. These studies indicate that conjugation of a cytotoxic agent to a monoclonal antibody can confer on that agent selectivity for a particular target cell type which is recognised by the antibody.

Animals↗
PubMed1983

Chronic hyperamylasemia and chronic pelvic inflammatory disease.

A 54-year-old woman with chronic pelvic inflammatory disease and pyelonephritis developed persistent hyperamylasemia with transient increases in the amylase-creatinine clearance ratio. Even though chronic pancreatitis was suspected clinically, at postmortem examination the pancreas was found to be normal. We suggest that the hyperamylasemia resulted from entry into the circulation of amylase produced within sequestered endosalpingeal epithelial cysts, possibly amplified by impaired renal clearance. Thus, the potential of the serum amylase assay as a sign of serous ovarian tumors is further indicated.

Amylases↗
PubMed1982

Expression of the ROAM mutations in Saccharomyces cerevisiae: involvement of trans-acting regulatory elements and relation with the Ty1 transcription.

The regulatory mutations in Saccharomyces cerevisiae designated cargA + Oh, cargB + Oh, and durOh are alterations in the control regions of the respective structural genes. The alteration causing the cargA + Oh mutation has been shown to be an insertion of a Ty1 element in the 5' noncoding region of the CAR1 ( cargA ) locus. All three mutations cause overproduction of their corresponding gene products and belong to the ROAM family of mutations (Regulated Overproducing Allele responding to Mating signals) in yeast. The amount of overproduction in ROAM mutants is determined, at least in part, by signals that control mating functions in yeast. We report the identification of two genetic loci that regulate Oh mutant gene expression but that do not affect mating ability. These loci are defined by the recessive roc mutations ( ROAM mutation control) that reduce the amount of overproduction caused by the cargA + Oh, cargB + Oh, and durOh mutations. RNAs homologous to CAR1 ( cargA ), DUR1 ,2 and Ty1 DNA probes were analyzed by the Northern hybridization technique. In comparison with wild-type strains, cargA + Oh and durOh mutant strains grown on ammonia medium contain increased amounts of CAR1 and DUR1 ,2 RNA. This RNA overproduction is diminished in MATa/MAT alpha diploid strains as well as in haploid strains that also carry the ste7 mutation which prevents mating or that carry either of the roc1 or roc2 mutant alleles. The amount of RNA homologous to Ty1 DNA is also reduced in ste7 , roc1 , and roc2 mutant strains. This reduction is not observed in a strain with the ste5 mutation, which prevents mating but has no effect on overproduction of ROAM mutant gene products.(ABSTRACT TRUNCATED AT 250 WORDS)

Allophanate Hydrolase↗
PubMed1982

Release of Mycoplasma pneumoniae substances after phagocytosis by guinea pig alveolar macrophages.

Antibody-opsonized Mycoplasma pneumoniae cells with various radioactive markers were sedimented onto monolayers of guinea pig alveolar macrophages (AM). After 2 h of incubation, about 50% of the activity of [3H]palmitate-labeled mycoplasmas was associated with AM. Nonspecific attachment of the opsonized mycoplasmas to AM-free plastic surface areas was negligible. The occurrence of phagocytosis was proven by electron microscopy and monitoring of AM surface-bound antigen by 125I-labeled F(ab)2 fragments. The activity of [3H]palmitic acid-labeled mycoplasmas was only slowly released into the supernatant. About 55% of the activity remained AM-associated up to 70 h after phagocytosis. After phagocytosis of [3H]thymidine-labeled cells, about 70% of the radioactivity found non-precipitable by trichloracetic acid. 3H-amino acid-labeled protein was released to 50% within 8 h. Supernatants and AM were tested for M. pneumoniae antigen with enzyme-linked immunosorbent assay. Considerable amounts of antigenically active material could be found in the supernatant within 8 h. This antigen was totally inactivated by heat (80 degrees C). Trypsin treatment (1 mg/ml, 10 min) reduced the antigenicity by 80%. The results suggest a selective release of microbial material after phagocytosis.

Animals↗
PubMed1981

Determination of trace amounts of nitrites in fabricated nonmeat products.

Low levels of nitrite (1-5 ppm) contributed by raw materials in new fabricated food products were successfully determined by a modification of an AOAC method for processed meats. Recoveries were greater than 90% for composite samples to which 5-10 ppm nitrite had been added. This method allows analyses of fabricated food products containing hydrogenated vegetable oils, soy proteins, and dried egg whites for low levels of nitrite.

Food, Formulated↗
PubMed1981

Phagocytosis and complement action.

THe interaction of pathogenic mycoplasmas with two components of the "nonspecific" defence system is influenced by the lack of a cell wall and perhaps the tight attachment to host cells. On mycoplasmas, complement can act directly on the parasite membrane surface and cause damage comparable to the effects on animal cells, namely lysis and death. Results with Mycoplasma pneumoniae suggest a direct activation by this species of the complement sequence without participation of homologous antibody. Activation may occur via the alternate pathway and perhaps even by direct triggering of the classical pathway. The action results in rounding, opsonization and death of some or all of the cells. Since complement components have been found in bronchial washings, this direct activation may be of some importance in the first stages of infection. Furthermore, it sufficiently explains the fact that M. pneumoniae is found only on the surface but not in the deeper tissues of the respiratory tract even in severe infections. The interactions of mycoplasmas with phagocytes, one of the first lines of defence against infection, is of considerable interest. Mycoplasmas seem to be relatively resistant to phagocytosis as long as they are not opsonized. They have been observed attaching to macrophage surfaces without being ingested. Addition of homologous antibody triggered immediate engulfment and intracellular killing. The aspects of interaction of phagocytes with mycoplasmas are even more interesting because in most cases the mycoplasmas which have to be phagocytized are attached to the surface of other tissue cells. This raises the problem of secondary damage caused by the enzymes of the phagocytizing cell. Our knowledge about the mycoplasma-phagocyte-interaction is scarce and the experimental approaches are difficult.

Animals↗