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Biomedical subjects

S Argov

Publications and source records attributed to S Argov.

At least 73 records · Page 4Linked to original sources

Tumor biopsy cells participating in systems in which cytotoxicity of lymphocytes is generated. Autologous and allogeneic studies.

Freshly separated tumor cells from sarcomas and carcinomas were used in various roles in lymphocyte-target cell interaction assays. They were poorer allogeneic stimulators than lymphocytes. They were however good allotargets for the cytotoxicity generated in mixed lymphocyte cultures. They were also killed as third party targets by lymphocytes activated in MLC. In a proportion of experiments, lymphocytes activated in MLC killed autologous tumor cells. Autotumor killer effect was generated in the majority of mixed cultures containing lymphocytes and tumor biopsy cells from the same individual. Generation of cytotoxicity against K562 was a good measure of lymphocyte activation and could be used as a sensitive indicator for the occurrence of the recognition step in the mixed cultures. We propose that for the search of lymphocytes with specific receptors, activation is a more reliable parameter than specific cytotoxicity since the latter function is also influenced by the sensitivity of the target. The results confirmed that patients with carcinomas and sarcomas possess autotumor-reactive lymphocytes. These can be activated for cytotoxicity by in vitro confrontation with the tumor cells and occasionally through stimulation which is unrelated to the tumor cells.

Adolescent↗

Incidence and type of tumors induced in C57BL bg/bg mice and +/bg littermates by oral administration of DMBA.

As an attempt to study the effect of the beige (bg) mutation on chemical carcinogenesis, 65 C57Bl/bg/bg mice and 83 +/bg littermate controls received DMBA in five weekly intragastric doses. The incidence of tumors of different histological types was monitored through observation periods ranging between 165 and 500 days. By 165 days after the first DMBA feeding, 18% of the +/bg and 31% of the bg/bg mice had developed tumors. The beige mice had a higher incidence of epithelial and non-epithelial tumors arising in cutaneous or subcutaneous sites than the controls. The total incidence of lymphomas was similar in the two groups. However, lymphomas appeared somewhat earlier in beige than in control mice. Altogether 33 +/bg and 27 bg/bg mice were followed for 500 days. By this time, 73% of the +/bg and 78% of the bg/bg mice had developed tumors. The beige group showed a higher incidence of non-thymic lymphomas than the controls. In contrast, the incidence of thymic lymphoma, cutaneous epithelial tumors and bile-duct adenomas was similar in the two groups or higher in +/bg that in bg/bg mice. The results suggest that the bg mutation causes a certain defect in a mechanism that may prevent or delay the onset of non-thymic lymphomas and of epithelial and non-epithelial cutaneous tumors in DMBA-treated mice. The differences between the two groups were smaller than those previously reported in relation to the increased susceptibility of beige mice to certain transplanted tumors, attributed to the known defect in natural killer (NK) activity in the beige mice. The reduced differential in the DMBA system may be due to the partial reduction of NK activity, induced by the carcinogen, as reported previously (Ehrlich et al., 1980) and confirmed in the present study.

9,10-Dimethyl-1,2-benzanthracene↗

Is routine crossmatching for two units of blood necessary in elective surgery?

The usual preparation for many elective procedures calls for typing and crossmatching for 2 units of blood. Most of the blood prepared is not used. Every unit of blood kept for a specific patient is removed from the blood bank pool, thereby reducing its resources. Fourteen hundred of the most frequent elective operations were examined with regard to their blood utilization. A transfusion index was developed to determine whether preoperative crossmatching was justified. Applying the index to 1,400 elective procedures, it was found that only vascular procedures justified preoperative crossmatching. The safety of transfusion (elective and emergency) based on type and antibody screening is explained. The constant increase in blood consumption (as for open heart surgery) and the small increase in blood donations has created a blood shortage. It is suggested that surgeons stop requesting crossmatching for 2 units for those elective procedures in which blood is rarely used. This would decrease the workload in the blood bank and increase the blood bank pool without compromising patients' safety.

Blood Grouping and Crossmatching↗

Human tumor-lymphocyte interaction in vitro. VII. Blastogenesis and generation of cytotoxicity against autologous tumor biopsy cells are inhibited by interferon.

In a high proportion of cases blood lymphocytes from cancer patients cultured with autologous tumor biopsy cells undergo blastogenesis. In addition, cytotoxicity against autologous tumor cells is generated. These autoactivated lymphocytes also kill the highly NK-sensitive K-562 and Molt-4 cells. Addition of interferon (IF) at the initiation of the cultures inhibited blastogenesis and the generation of autologous cytotoxicity. On the other hand, lymphocytes already activated for autologous killing in the mixed cultures were not affected by short-term IF treatment prior to the cytotoxic assay. Lymphocytes cultured alone lose their cycotoxicity against K-562. However, when IF was present in these cultures the lymphocytes were cytotoxic for K-562. In addition, lymphocytes cultured for 6 days under conditions which did not result in activation killing of Molt-4 cells could be induced by short-term incubation of the effectors with IF.

Cell Line↗

Is routine use of the nasogastric tube justified in upper abdominal surgery?

Three hundred patients who underwent upper abdominal operations were studied. One hundred fifty patients were treated by insertion of a nasogastric tube, and 150 patients were treated without it. The incidence of postoperative pneumonia was 10 times higher in the patients treated with a nasogastric tube. Pneumonia was directly related to the patient's age and the duration of the tube's use. In view of the disadvantages and complications of the nasogastric tube, its routine use appears unjustified. It should be reserved as a tool for treating postoperative complications such as paralytic ileus and acute gastric dilatation.

Abdomen↗

Target-effector cell interaction in the natural killer cell system. V. Energy requirements, membrane integrity, and the possible involvement of lysosomal enzymes.

Various inhibitors were used to study further the mechanism of natural killing and to compare it to lympholysis by cytotoxic T lymphocytes (CTL). The respiratory inhibitors DNP and NaN3 or low temperatures (0 degrees) blocked the cell contact phase of target-effector interaction in the CTL system but not the NK system. The lytic stage was also inhibited by the glycolytic inhibitors, iodoacetate and NaF, in the NK system as previously shown in the CTL system. Dimethylsulphoxide, a dipolar solvent, and cytochalasin B, a microtubule disruptor, inhibited NK target binding. Pre-treatment of Nk cells with glutaraldehyde, a protein cross-linking agent, completely prevented lysis, but not the formation of target-effector conjugates. The lytic phase of NK lysis was inhibited by chloroquine which also inhibited lysosomal enzyme function. Lysosome defective, beige mutant mice were also totally deficient in NK lytic function and this defect could not be restored with cGMP. T-cell and macrophage mediated cytolysis was previously shown to be relatively normal in beige mice. These results suggest that (i) the mechanism of NK cytolysis is a complex, multistep process, and (ii) this process is fundamentally different from that occurring in CTL. A 'stimulus-secretion' model of NK cytolysis is presented in which it is postulated that lysosomal enzymes may be the lytic molecules.

Animals↗

Prolonged post-vagotomy gastric atony treated by oxytocin.

Persistent and complete post-vagotomy gastric atony was treated in 3 patients by intravenous infusion of oxytocin. Despite failure of both conventional treatment with gastric aspiration and intravenous fluids or jejunal feeding, as well as the reported trials with bethanechol chloride and metaclopramide, these patients promptly responded to oxytocin. It appears that the latter may represent a solution to this uncommon but recalcitrant complication of peptic ulcer surgery.

Chronic Disease↗

Cation requirement of natural, in-vitro generated and antibody dependent killing exerted by human lymphocytes.

Three cytotoxic systems, NK, ADCC and the seemingly indiscriminative cytotoxicity of in vitro activated lymphocytes (cultivated with K 562) were found to require Ca++ and did not function in Mg++. The optimum concentration of Ca++ was identical for the three systems and for various lymphocyte subsets. 15 minutes after initiation of the interaction cell damage had already occurred in all three systems.

Animals↗

Natural cytotoxicity in man: activity of lymph node and tumor-infiltrating lymphocytes.

Lymphocytes from blood, lymph node and tumor have been tested for cytotoxicity against the K562 cell line which is known to be highly sensitive to lysis by spontaneously reactive cells. Cytotoxicity was found in all 13 samples from healthy donors and in 17/32 cancer patients. By contrast, activity was determined in only 1/18 lymph node and 1/14 preparations of tumor-infiltrating lymphocytes. Lymph node cells were similarly nonreactive against 3 other cell lines known to be sensitive to natural cytotoxicity. Studies of the composition of the effector populations revealed no absolute deficit of a particular cell type although there were differences between them resulting from the different isolation procedures used. Enrichment of the lymph node population for non-T, non-B lymphocyte was ineffective in inducing cytotoxicity in previously nonreactive samples although this procedure uniformly increased the cytotoxic potential of blood lymphocytes. Tests with blood taken during operation showed that the lack of reactivity in these preparations was unlikely to be a result of the effects of anesthesia or surgery. The reason for the low cytotoxicity in the lymph node and tumor-infiltrating lymphocytes is as yet undefined.

Anesthesia↗

Fourier transform infrared microspectroscopy as a quantitative diagnostic tool for assignment of premalignancy grading in cervical neoplasia.

The early diagnosis and proper identification of cervical squamous intraepithelial lesions plays an important role in a good prognosis for the patient. However, the present practice of screening based on PAP (Papanicolaou) smear and histopathology makes it tedious and prone to human errors. We assess the validity of FTIR microspectroscopy (FTIR-MSP) of biopsies as a method to properly assign the correct stage of premalignancy in patients with symptoms of cervical intraepithelial neoplasia. For the first time we evaluate the biopsies based on the FTIR spectra for different grades of neoplasia in tandem with probabilistic neural networks (PNNs) and histopathology. The results show that the grading of neoplasia based on FTIR-MSP and a PNN differentiates the normal from premalignant with a high level of accuracy. The false positive identification of the normal as cervical intraepithelial neoplasia 1 (CIN1), CIN2, and CIN3 patients is 9.04, 0.01, and 0.01%, respectively. The false negative identification of CIN2 patients as normal and CIN1 patients is 0.01 and 4.4%, respectively. Similarly, the false negative identification of CIN3 patients as normal, CIN1, and CIN2 is 0.14, 6.99, and 9.61%, respectively. The small errors encountered in the grading are comparable to current methods, encouraging advanced studies for the development of mechanized equipment for the diagnosis and grading of premalignant cervical neoplasia.

Algorithms↗

Can Fourier transform infrared spectroscopy at higher wavenumbers (mid IR) shed light on biomarkers for carcinogenesis in tissues?

Fourier transform infrared microspectroscopy (FTIR-MSP) has shown promise as a technique for detection of abnormal cell proliferation and premalignant conditions. In the present study, we investigate the absorbance in the sensitive wavenumber region between 2800 and 3000 cm(-1), which has been known to be due to the antisymmetric and symmetric stretching vibrations of CH2 and CH3 groups of proteins and lipids. We report common biomarkers from this region that distinguish between normal and malignant tissues and cell lines. Based on our findings, we propose that the wavenumber region around 2800 to 3000 cm(-1) in the FTIR spectra of cells and tissues could provide valuable scientific evidence at the onset of premalignancy and may be used for ex vivo and in vitro detection of carcinogenesis. To further examine the utility of these markers in cancer diagnosis and management, they are tested successfully in monitoring the changes occurring in leukemia patients during chemotherapy.

Animals↗