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Biomedical subjects

P Kahn

Publications and source records attributed to P Kahn.

At least 55 records · Page 3Linked to original sources
PubMed1984

Transformation of mammalian fibroblasts and macrophages in vitro by a murine retrovirus encoding an avian v-myc oncogene.

A murine retrovirus which expresses the avain v-myc OK10 oncogene was constructed. The virus, denoted MMCV, readily transforms fibroblasts of established lines, such as mouse NIH/3T3 and rat 208F cells, to anchorage-independent growth in agarose. The virus also transforms primary mouse cells: (i) virus-infected macrophages are induced to form large colonies in semi-solid media, and can easily be expanded into mass cultures; (ii) MMCV-infected fibroblastic cells from mouse limb buds undergo morphological transformation and grow in semi-solid medium. MMCV thus transforms both mouse fibroblastic cells and macrophages in vitro, in a fashion similar to the v-myc-containing avian viruses in chicken cells. The possibility of introducing a transforming myc gene into mammalian cells by virus infection provides a novel approach for studying the mechanism of myc transformation in cells from many lineages.

Animals↗
PubMed1984

Ts mutants of E26 leukemia virus allow transformed myeloblasts, but not erythroblasts or fibroblasts, to differentiate at the nonpermissive temperature.

The myb, ets-containing avian acute leukemia virus E26 transforms myeloblasts, erythroblasts, and fibroblasts in culture and causes a mixed erythroid/myeloid leukemia in chicks. We report the isolation and characterization of four E26 mutants that are temperature-sensitive (ts) for myeloblast transformation. At the permissive temperature, tsE26-transformed myeloid cells resemble macrophage precursors and proliferate rapidly, provided the growth medium contains chicken myelomonocytic growth factor (cMGF). When shifted to the nonpermissive temperature the cells stop growing and differentiate into macrophage-like cells, as determined by their expression of morphological, functional, and antigenic markers of normal macrophages. They also lose their responsiveness to cMGF and secrete a cMGF-like factor. Ts mutants of E26 retain their leukemogenicity and their ability to transform both erythroblasts and fibroblasts at the nonpermissive temperature, suggesting that the myb oncogene of E26 causes myeloblast transformation and that ets is responsible for erythroblast and fibroblast transformation.

Animals↗
PubMed1984

src- and fps-containing avian sarcoma viruses transform chicken erythroid cells.

We report here that several oncogene-transducing avian sarcoma virus strains, namely Rous sarcoma virus (src), Fujinami sarcoma virus (fps), and PRCII (fps), transform avian erythroid cells in vitro and in vivo. The src- and fps-transformed erythroblasts grow in vitro for 20-30 generations, require special growth conditions, and tend to differentiate spontaneously. In these properties, they resemble erythroid cells transformed with the erbB-containing H strain of avian erythroblastosis virus (AEV-H) but differ from those transformed with AEV-ES4 (erbA, erbB), which grow under standard culture conditions and rarely differentiate spontaneously. Erythroblasts transformed with viruses carrying temperature-sensitive mutations in the src or fps oncogene and then shifted to the nonpermissive temperature in the presence of anemic serum (as a source of an erythropoietin-like factor) differentiate terminally into erythrocytes. These results demonstrate that several members of the src gene family other than erbB have the capacity to transform erythroid cells.

Animals↗
PubMed1984

[Free thyroxine in routine diagnosis].

In our hospital the measurement of free thyroxine with the Amerlex FT4-RIA has become a well-established routine screening method. Compared with the determination of total thyroxine we were able to reduce the number of all supplementary thyroid-specific tests, particularly of TBG, by 30%. Even the frequency of triiodothyronine tests decreased whereas the TSH-levels increased slightly. This is probably an indication of a better diagnosis of incipient hypothyroidism. Especially FT4-values in patients undergoing heparin treatment should be interpreted with special care. By changing from total thyroxine to FT4 we have reduced the department's expenditure by about AS 250 000,- annually, without impairing the accuracy of our diagnostics. Compared with former test combinations, specificity and accuracy have improved.

Austria↗
PubMed1983

Tumorigenicity of SV40-transformed human and monkey cells in immunodeficient mice.

Human cells transformed in vitro by SV40 to the anchorage-independent state rarely form tumors in nude mice and therefore constitute an important exception to the otherwise tight correlation between anchorage independence and cellular tumorigenicity. In this paper we explore a number of possible explanations for this unusual situation. We find that the phenomenon is not restricted to human cells but includes monkey cells as well. The nontumorigenic phenotype of the primate SV40 transformants is highly stable. We are unable, through selection of ever more anchorage-independent lines, to generate a primate SV40 transformant which will grow as a tumor in even the most immunologically crippled animals. One tumor was obtained from SV80 (an SV40-transformed human cell line) following injection into a mouse deficient in both T and B cell functions. However, cell lines derived from this tumor are not significantly more tumorigenic than the SV80 parent. This low incidence of tumor formation is not due to the fact that the primate cells are transformed by nononcogenic defective viral genomes nor to a nutritional inadequacy of the host animal for the growth of human cells. Although a T cell-independent mechanism may be the major mechanism involved in tumor suppression, it is unlikely that this completely accounts for the general lack of tumor growth by most of these cells. It appears that the interaction of SV40 (a primate virus) with primate cells may be intrinsically less oncogenic than its interaction with rodent cells.

Animals↗
PubMed1983

Quail embryo fibroblasts transformed by four v-myc-containing virus isolates show enhanced proliferation but are non tumorigenic.

Quail embryo fibroblasts infected with any of the four natural avian myc gene-containing virus strains (MC29, CMII, OK10 and MH2) or with the myb, ets-containing E26 acute leukemia virus, were examined for their expression of several transformation-associated parameters. All myc-containing viruses, but not E26 or Rous sarcoma virus (used as a control) induced a dramatic stimulation of cell proliferation. In addition, the myc virus-transformed cells exhibited prominent nucleoli, possibly as a consequence of their increased proliferation. Cells transformed by MC29, OK10, MH2 and E26 were capable of growing in semi-solid medium and showed a loss of actin cables and, in most cases, of an ordered fibronectin distribution. All of the myc virus-transformed fibroblasts, as well as the E26-transformed cells, were unable to form tumors in nude mice, indicating that the myc gene (and the myb/ets genes) are not sufficient for the induction of a fully malignant phenotype in avian fibroblasts.

Animals↗
PubMed1983

Structural correlates of cellular tumorigenicity and anchorage independence in transformed fibroblasts.

The ability on nonhematopoietic cells to proliferate in vitro without attachment to a solid surface (anchorage independence) is known to be highly correlated with their ability to form tumors in nude mice. Transformed cells in vitro frequently also show less organization of the intracellular actin-containing microfilament bundles and less cell-surface fibronectin compared to normal cells. We have examined whether the loss of the anchorage requirement for growth is related to either of these structural changes in the cellular cytoskeleton. Our approach was to select a series of subclones from a nontransformed Syrian hamster fibroblast line, NIL8, for the acquisition of either anchorage independence in vitro or tumorigenicity in nude mice. These subclones were then examined for concomitant changes in the cytoskeletal structures. We found that anchorage independence, decreased actin cable organization, and tumorigenicity in nude mice were coordinately induced in both the in vitro- and in vivo-selected subclones, whereas the loss of fibronectin was not consistently coinduced with these three markers. These results suggest that the transformation-associated decrease in actin cable organization in this type of cell enhances the ability to grow without anchorage in vitro and to form tumors in vivo.

Actins↗
PubMed1982

Tumorigenicity of partial transformation mutants of Rous sarcoma virus.

Chicken embryo cells infected with partial transformation mutants of Rous sarcoma virus were tested for tumor-forming ability in chickens and in nude mice. Cells transformed by each of these partial transformation mutants display different combinations of transformation parameters. They therefore present a potentially favorable system for analyzing which properties of transformed cells are necessary for tumor formation. We found that the relative tumorigenicity of the virus mutants was generally similar in chickens and in nude mice, except that certain temperature-conditional mutants appeared to be sensitive to the differences in body temperature of the two experimental animals. (The body temperature of nude mice is 4 to 5 degrees C lower than that of chickens). Thus, the nude mouse appears to be a suitable system for testing the tumorigenicity of transformed chicken cells. Because mice are nonpermissive for Rous sarcoma virus infection and replication, it was possible to recover the transformed chicken cells from the tumors in this host and to determine what phenotypic changes they had undergone during tumor development. We also examined the relationship between various cellular properties of the virus-infected chicken cells in vitro and their tumorigenicity in nude mice. The combined results of these two studies indicated that anchorage independence and plasminogen activator production were highly correlated with the tumor-forming ability of these cells, whereas loss of fibronectin did not correlate with tumorigenicity. Furthermore, the inability of the least tumorigenic virus mutant to stimulate the phosphorylation of a 36,000-Mr target of pp60src raises the possibility that the 36,000-Mr protein plays a role in tumor formation.

Animals↗
PubMed1981

[99mTc-pyrophosphate myocardial scintigraphy in patients with chronic stable angina pectoris (author's transl)].

In 66 patients suffering on chronic stable angina pectoris myocardial scintigrams with 99mTc-pyrophosphate were evaluated. Patients who had former infarcts or infarct signs in ECG were excluded. 16 normal subjects were used as controls. In all normal subjects and in 35 patients with chronic A.P. a normal myocardial scintigram could be obtained. In the remaining 31 patients a localized myocardial tracer accumulation could be seen. There was a correlation between the tracer accumulation and the limitted left ventricular function. No correlation was found between the severity and the number of involved coronary arteries and a positive scintiphoto. The mechanism of the tracer accumulation is discussed. The results of this investigation show that a positive myocardial scintigram does not prove a myocardial infarction. It is a sign for a insufficiency of the contractility of the left ventricle, probably due to under perfusion.

Angina Pectoris↗
PubMed1981

Familial late onset oculopharyngeal muscular dystrophy.

An English family is described several members of which have suffered from oculopharyngeal muscular dystrophy. No symptoms were noticed in any affected members of the family until aged at least 50 years. An autosomal dominant pattern of inheritance is clearly shown.

Age Factors↗
PubMed1981

[Assessment of the results of aorto-coronary bypass surgery with the technetium 99m pyrophosphate scintigram (author's transl)].

In 40 patients with angiographically-documented coronary artery disease, technetium 99m pyrophosphate (99mTc-PYP) myocardial scintigrams were obtained prior to and four to six weeks after aorto-coronary bypass surgery. In the majority of patients, preoperative and postoperative exercise testing with simultaneous pulmonary artery pressure recordings was performed. In 22 of 30 patients with preoperatively increased 99mTc-PYP myocardial activity, no tracer accumulation could be found postoperatively. In the latter patients, there was also a significant increase in exercise capacity and lessening of ischemic ST-segment depression in the exercise ECG. In the remaining eight patients in whom increased tracer accumulation was found to persist postoperatively, there was no improvement in exercise capacity. In ten patients with no myocardial tracer accumulation preoperatively, unchanged myocardial scintigrams and a significant decrease of the ischemic ST-segment depression in the exercise ECG were seen postoperatively except in one patient with perioperative myocardial infarction. These results were also partially confirmed by repeated coronary angiography and ventriculography. Patent bypass grafts were associated with regional improvement in left ventricular function. The results indicate that postoperative absence of myocardial tracer accumulation appears due to amelioration of preexisting myocardial ischemia at rest. Thus, in the assessment of the results of aorto-coronary bypass surgery, the 99mTc-PYP scintigram offers an important diagnostic potential.

Coronary Artery Bypass↗
PubMed1980

[Serum myoglobin and myocardial infarction (author's transl)].

The serum myoglobin level was determined in 45 healthy persons and 64 patients of whom 43 had a recent proven myocardial infarct. The normal myoglobin value was found to ae 43.7 +/- 16.0 ng/ml. All the patients with myocardial infarct who had been transferred to our Coronary Care Unit showed raised serum myoglobin levels already 4 hours after symptoms commenced, the maximum being reached after 10 hours. 20 hours after myocardial infarction normal values were once again registered. Pathological serum myoglobin levels were also found without infarction after skeletal muscle damage in the course of resuscitation measures, or after operations or in renal failure. The value of the serum myoglobin concentration in the diagnosis of myocardial infarction lies in the early elevation of this parameter, but it is unspecific and the method is relatively laborious.

Creatine Kinase↗
PubMed1980

[New aspects on diagnosis and therapy of primary hyperparathyroidism (author's transl)].

26, out of them 20 surgically proven cases of primary hyperparathyroidism are presented. The value of different laboratory, radiographic and scintigraphic analysis is examined. The estimation of calcium and phosphate in serum, the iPTH-determination and fine detail hands radiographs were found to be sufficient to establish diagnosis and indication for surgery. The chloride/phosphate-ratio proved valuable in comparative statistical analysis between pHPT and two control groups. Venous sampling at present seems to be the superior method for preoperative localization of parathyroid disease. It should be performed before second surgical intervention in the cervical region, in elderly (more than 60 years old) and risk patients. Early diagnosis and therapy of pHPT is important as pHPT is a chronic disease with many organ complications. The value of calcium-screening in an age group between 40 and 60 years is discussed.

Aged↗
PubMed1980

[Clinical usefulness of 67 gallium scintigraphy in malignant lymphoma].

The results of 67-gallium scanning in 644 patients with histological confirmation of diagnosis are presented. 67-Ga uptake was recorded in 93.3% of 312 malignant and in 85.8% of 332 benign conditions. In 89.4% 67-Ga was successful in distinguishing between malignant and benign disorders. In 58 of 62 lesions due to malignant lymphoma 67-Ga uptake was seen. 67-Ga scanning is an indispensable tool for early diagnosis of hepatoma (n = 80) and an important non-invasive staging procedure for lymphoma patients which complements exploratory laparotomy.

Diagnosis, Differential↗
PubMed1979

Cellular tumorigenicity in nude mice. Test of associations among loss of cell-surface fibronectin, anchorage independence, and tumor-forming ability.

Fibronectin (FN; also called large external transformation-sensitive [LETS] protein or cell-surface protein [CSP]) is a large cell-surface glycoprotein that is frequently observed to be either absent or greatly reduced on the surfaces of malignant cells grown in vitro. Because FN may be a useful molecular marker of cellular malignancy, we have carried out an extensive screening to test the specific association among the degree of expression of FN, anchorage-independent growth, and tumorigenicity in the athymic nude mouse. A variety of diploid cell strains and established cell lines were tested for the expression of surface FN by indirect immunofluorescence using rabbit antisera against human cold insoluble globulin, rodent plasma FN, or chicken cell-surface FN. Concomitantly, the cells were assayed for tumor formation in nude mice and for the ability to form colonies in methylcellulose. Tumorigenic cells often showed very low surface fluorescence, confirming earlier reports. However, many highly tumorigenic fibroblast lines from several species stained strongly with all three antisera. In contrast, the anchorage-independent phenotype was nearly always associated with tumorigenicity in approximately 35 cell lines examined in this study. In another series of experiments, FN-positive but anchorage-independent cells were grown as tumors in nude mice and then reintroduced into culture. In five of the six tumor-derived cell lines, cell-surface FN was not significantly reduced; one such cell line showed very little surface FN. Our data thus indicate that the loss of cell-surface FN is not a necessary step in the process of malignant transformation and that the growth of FN-positive cells as tumors does not require a prior selection in vivo for FN-negative subpopulations.

Animals↗