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Biomedical subjects

M Janowski

Publications and source records attributed to M Janowski.

At least 19 recordsLinked to original sources

Effect of neutrons alone or combined with diethylnitrosamine on tumor induction in the livers of infant C57BL mice.

The possible combined effects of the initiator diethylnitrosamine (DEN)+neutrons on the induction of foci, adenomas and carcinomas in the livers of C57BL/Cnb mice were evaluated. Four groups of infant mice were treated as follows: DEN alone, neutrons alone, DEN followed by neutrons and neutrons followed by DEN. Ten mice in each group were killed at 10-week intervals over 70 weeks. The following parameters were measured: body weight, liver weight, number and size of superficial macroscopic liver lesions, and number and total surface area of the different types of microscopic liver lesions. The rate of appearance of foci increased significantly at different times when a dose of 0.125 Gy of neutrons was administered 7 days before or after a dose of 1.25 micrograms of DEN. No significant differences were observed in the total surface area of foci and/or adenomas and carcinomas when increasing doses of neutrons were given 7 days before or after the administration of 1.25 and 2.5 micrograms of DEN.

Animals↗

[Type II carnitine palmitoyl transferase deficiency complicated by acute respiratory failure].

Carnitine palmitoyl transferase (CPT) deficiencies can realise distinct clinical presentations. The best known is the muscular form with episodic muscle necrosis and paroxysmal myoglobinuria after prolonged exercise, in young adults, and results from decreased CPT II activity. In this paper, we report on an observation of a patient with a severe CPT II deficiency who presented a respiratory failure during an attack of muscle necrosis. The severity of the symptomatology were associated with a conspicuous reduction of CPT II residual activity in leucocytes and in fibroblasts. Fasting test showed an hypoketogenesis. These results support the concept that CPT II deficiency is ubiquitous, even though injury is restricted to the skeletal muscle.

Adolescent↗

Effect of X rays alone or combined with diethylnitrosamine on tumor induction in infant mouse liver.

The possible combined effects of the initiator diethylnitrosamine (DEN) with X rays on cancer induction in C57BL/Cnb mouse liver were evaluated. Four groups of infant mice were treated as follows: with DEN alone, with X rays alone, with DEN + X rays, and with X rays + DEN. Mice in each group were killed at 10-week intervals over 70 weeks. The following parameters were measured: body weight, liver weight, number and size of macroscopic liver lesions, and number and total surface of the different types of microscopic liver lesions. The number of induced liver foci and carcinomas was found to depend essentially on the dose of DEN. X irradiation did not produce any combined effect on the induction of foci and carcinomas when given 7 days before or after DEN administration.

Animals↗

Unexplained fever and chronic fatigue: abnormal circadian temperature pattern.

OBJECTIVES: Standard clinical and biological investigations can be used to determine the origin of persistent and moderate fever in a large number of otherwise asymptomatic patients. However, in a small proportion of cases, isolated fever and fatigue persist despite the absence of detectable organic malfunction. This study was conducted to investigate the circadian thermic pattern in patients with apparently unexplainable fever and chronic fatigue and in those with fever of recognized origin. METHODS: We recorded central temperature continuously for 24 hours in patients with moderate fever of both unexplained and recognized origin, and in a control group of healthy volunteers. A Fourier series was used for harmonic analysis. RESULTS: Thermic patterns specific to the three groups were identified by statistical and factorial analysis. The patients with fever of unknown origin and chronic fatigue were clearly characterized in terms of the phase, amplitude of the first (fundamental) harmonic and minimum circadian temperature. CONCLUSION: The abnormal central temperature pattern in these patients may prove to be an important step in the management of febrile patients.

Adolescent↗

Protamine allergy reactions during cardiac catheterization and cardiac surgery: risk in patients taking protamine-insulin preparations.

Protamine insulin use may immunologically sensitize patients to protamine, leading to anaphylactoid reactions upon subsequent exposure to protamine sulfate during cardiac catheterization or cardiovascular surgery. The risk of such reactions in protamine insulin-dependent patients is uncertain. One catheterization study reported a 50-fold greater risk while a second showed no increased risk! To clarify the risk, the records of 7,750 cardiac catheterization procedures between 1984 and 1987 were analyzed for presence of NPH or PZI insulin use, protamine administration, and any complications or adverse reactions. Protamine was administered in 3,341/7,750 procedures (43%), including 171 in diabetics receiving NPH insulin. Adverse reactions to protamine occurred in 2/3, 170 noninsulin patients, 0.06%, and adverse reactions due to probable NPH insulin sensitization occurred in 1/171, 0.6%, of NPH diabetics, p = .034. Meta-analysis of risk showed an odds ratio of 7.96 for the NPH diabetic patients, and combining these results with the other large series in the literature (269 NPH diabetics total) showed an odds ratio of 4.19 compared to a non-NPH insulin group. Meta-analysis of the surgical literature showed the risk in surgical patients to be 2.1% in NPH patients versus 0.12% with no NPH, with an odds ratio of 15.52. The greater incidence in surgical patients may be due to protamine sensitization at prior catheterization and to the larger dose of protamine administered to surgical patients.

Anaphylaxis↗

ras proteins and the ras-related signal transduction pathway.

Mammalian ras genes may naturally acquire oncogenic transformation potential through some point mutations which result in the impairment of the normal ras protein functions, and which are localised in codons 12, 13 or 61. Mutationally activated ras alleles were found in a wide variety of human and carcinogen (including radiation)-induced animal malignancies. In man, myeloid leukemias are often associated with the presence of a mutationally activated ras gene (for review, see Bos JL (1989), Cancer Res 49:4682-4689). However, we failed till now in our attempts to detect oncogenic ras mutations in radiation-induced mouse myeloid leukemias. We thus have the feeling that ras might perhaps participate to tumorigenesis through another mechanism provoking a deregulation of the ras protein functions. In order to help evaluate such a possibility, we give here a very concise overview of the properties of the ras proteins and of their regulation by a variety of still hypothetical molecular switches. This overview does not include bibliographic references. Indeed, we gathered much of the information described below at the Cold Spring Harbor Symposium on "Function and Evolution of ras Proteins", May 9-13, 1990. Communications presented at Cold Spring Harbor Symposia may contain preliminary data and should not be cited in bibliographies. Another voluntary omission in this overview is that, for the sake of simplicity, we do not mention whether the data were obtained from experiments performed on H-, K- or N-ras. Details can be found in the published book of abstracts.

Animals↗

[Anti-hypertensive drugs prescribed to the elderly. Multicenter study at the hospital admission of 631 patients aged 70 plus years].

The anti-hypertensive treatment of 631 patients 70 years old and over was evaluated at the time of their hospitalization in 12 Internal Medicine departments in the western Paris suburbs, in May and June 1990. 49.6 +/- 3.9% received no such therapy; 30.3 +/- 3.6% were being treated for hypertension (group 1); 8.7 +/- 2.2% were taking anti-hypertensive drugs for poorly specified reasons (group 2); 11.4 +/- 2.5% were under such treatment for another reason. In groups 1 or 1 + 2, the most frequently prescribed medications were, in decreasing order: diuretics, calcium channel blockers, converting enzyme inhibitors, beta-blockers or central inhibitors. In the oldest patients, the beta-blockers were prescribed less and converting enzyme inhibitors more. More than half of the patients in groups 1 + 2 were taking a single drug. The most frequently prescribed combined therapy was diuretic + converting enzyme inhibitor. Our results seem to indicate that the prescription modalities depended, for the most part, upon an associated or suspected pathology, notably cardiac insufficiency.

Admitting Department, Hospital↗

The molecular biology of radiation-induced carcinogenesis: thymic lymphoma, myeloid leukaemia and osteosarcoma.

In mice, external X- or gamma-irradiation may induce thymic lymphomas or myeloid leukaemias, while bone-seeking alpha-emitters may induce osteosarcomas and, to a lesser extent, acute myeloid leukaemia. The present paper aims to review briefly some of the experimental data with respect to the molecular mechanisms underlying these radiation-induced carcinogenic processes. Thymic lymphomagenesis proceeds through an indirect mechanism. Recombinant proviruses often occur in the tumour cell DNA, favouring the idea that they might be involved. However, there are indications that they might mediate tumour growth rather than induction. It is plausible that activation of ras oncogenes by somatic point mutations might play a role in the carcinogenic process, although at a yet undetermined stage. Myeloid leukaemogenesis is characterized by a very early, putative initiating event, consisting of non-random rearrangements and/or deletions of chromosome 2. These may be related to deletions in the developmentally important homeobox gene clusters and to rearrangements of the sequences flanking the IL-1 beta gene. Either a gene of the homeobox family or IL-1 beta might be considered as potentially involved in the induction process. Osteosarcomagenesis in mice is often associated with the expression of proviruses, and the tumours often contain somatically acquired proviruses. These viruses may contribute to tumour development by affecting various growth-suppressor genes. Viruses isolated from bone tumours, although non-sarcomagenic, induce osteopetrosis, osteomas and lymphomas upon infection of newborn mice. Osteogenic tumours frequently display amplification of a region on mouse chromosome 15, which encompasses c-myc and Mlvi-1 sequences. Enhanced transcription of various oncogenes is found in individual tumours, but no specificity for osteosarcomas has been identified. In vitro systems of skeletoblast differentiation are being developed to study tumour induction in vitro.

Animals↗

Evidence of recombinant ecotropic provirus integration in thymic lymphomas induced by direct or indirect radiation effects.

Several investigators described the occurrence of ecotropic recombinant proviruses in the DNA of in-vivo or in-vitro propagated radio-induced lymphomas, but such proviruses were never detected in primary tumors. To assess their biological significance in the tumorigenic process, we reinvestigated the presence of new proviruses chiefly in primary radio-induced tumors and in models of radioleukemogenesis which could give additional support for their role. Such models included thymic lymphomas originating after (i) graft of non-irradiated thymuses in thymectomized irradiated mice and (ii) the injection of a B-ecotropic retrovirus (T1223/B) in association with a subleukemogenic dose of irradiation. We report for the first time that new ecotropic proviral sequences are encountered in a significant number (30%) of primary lymphomas induced directly by irradiation or indirectly in non-irradiated thymuses grafted in irradiated hosts. The existence of a 3.5-kbp Kpn1 restriction fragment with ecotropic sequences in the digested DNA of these tumor cells indicates that these new sequences belong to an ecotropic provirus recombinant in the gag-pol region. We observed that most of the primary radio-induced tumors in which novel recombinant provirus could be detected, displayed the integration at a single or at a few sites, demonstrating their clonality with respect to viral integration. The same was observed in thymic lymphomas arising after T1223/B virus injection and irradiation and in in-vivo or in-vitro propagated tumors. Altogether, these data bring the first evidence of the integration of ecotropic recombinant proviral genomes in a significant number of primary radiation induced thymic lymphomas and of their possible role in view of their frequent occurrence in grafted thymomas.

Animals↗

Failure to detect immune deficiency in rats after prenatal or early postnatal irradiation.

We have looked for medium-term sequelae in the immune system of rats that had been X-irradiated (0-2 Gy whole-body irradiation) during prenatal or early postnatal life. At an age of 8 weeks the histology of the spleen was normal, and so was the distribution of B and T lymphocytes. The serum immunoglobulin levels were not significantly altered, even when the different isotypes were considered. At an age of 10 weeks, the rats were immunized with a T-dependent or a T-independent dinitrophenylated-carrier antigen. Normal levels of specific antibodies were generated in all groups of animals injected with the T-independent antigen. The T-dependent response, in contrast, was higher in animals irradiated between day 6 and day 20 of gestation (but not in rats irradiated early after birth). This increase, however, was significant only for the IgM and IgG1 responses of some irradiated groups. Thus no medium-term immunodeficiency could be documented with the methods used. The alteration in a T-dependent response, however, points to a radiosensitive T regulatory mechanism.

Animals↗

Radiation leukemia virus: a marker for the study of intrathymic T cell differentiation.

Radiation Leukemia Virus (RadLV) is a retrovirus, which displays a highly specific thymotropism; after inoculation into young C57 BL/Ka mice, active virus replication is observed only in thymocytes and thymic lymphomas develop in most treated mice. The specific interaction between RadLV and the thymus resides in the particular susceptibility to infection of the most immature cells involved in the intrathymic lymphoid differentiation pathway and of non lymphoid thymic stromal cells. Recent data obtained from 'in situ' hybridization studies for detection of viral transcripts yield more detailed informations on these intriguing interactions.

Animals↗

Nucleotide sequence of a radiation leukemia virus genome.

The complete nucleotide sequence of an infectious molecular clone of a radiation murine leukemia proviral DNA RadLV/VL3(T+L+) has been determined. The sequence of the RNA genome is 8318 nucleotides long and contains three large open reading frames encoding the gag, pol, and env gene products. With the exception of a xenotropiclike R peptide and the LTR which bears structural similarities to a xenotropic LTR, displaying typical enhancerlike sequences, the remaining sequences are strikingly similar to the endogenous, ecotropic Akv murine leukemia virus. Therefore, it could be postulated that the leukemogenic properties of RadLV/VL3(T+L+) were generated by a recombination event between a xenotropic virus and an Akv-like ecotropic virus.

Base Sequence↗

[A minority of thymic lymphomas induced in the rat by a murine radioleukosis virus presents insertion in the vicinity of c-myc and a majority, a new nonviral polyadenylated RNA].

Thymic lymphomas were induced in rats either with the cell culture-propagated radiation leukemia virus complex, RadLV/VL3, or with a molecularly cloned isolate, RadLV/VL3 (T + L +). Four of thirty lymphomas, that were examined for rearrangements of the c-myc domain, displayed alterations in the vicinity of the c-myc gene, compatible with the idea of proviral integration. One of the tumours was investigated further, and was shown to contain a full length-proviral insert upstream of c-myc. Eight of nine lymphomas, that were investigated with respect to RNA expression, contained a novel polyadenylated RNA which could be detected with a molecular probe derived from the U5 portion of the retroviral long terminal repeat, but not with probes derived from the U3 portion or from the whole retroviral genome. These findings suggest that a RadLV/VL3 (T + L +) provirus can induce or activate RNA synthesis from c-myc by an enhancer mechanism, and from another cellular gene by a promotion mechanism.

Animals↗

Expression of protooncogenes in murine osteosarcomas.

The expression of 7 protooncogenes (c-sis, c-abl, c-mos, c-bas, c-Ki-ras, c-fos, c-myc) was examined in transplants and established cell lines from spontaneous and radiation-induced murine osteosarcomas. The transplant tumors were compared with different tissues, particularly skeletal tissue (sternum), and the osteosarcoma cell lines with fibroblast lines from the same mouse strains. C-sis was expressed above the level of controls in 2 osteosarcomas (TV, Os5). Three osteosarcomas showed over-expression of c-abl (TVK, DOS, Os5), c-bas (DOS, Os5 and V893) and c-fos (TVK, DOS, Os5), and 4 osteosarcomas showed over-expression of c-Ki-ras (TVK, DOS, Os5, Os16) and c-myc (TVK, DOS, TV, Os5). C-mos expression was not observed under the conditions used. One cell line (Os5) showed an altered transcript (1 kb transcript of c-fos). Apart from the relatively frequent increase in expression of the c-myc and c-ras-family, there was no indication that any particular protooncogene or combination of protooncogenes was associated with murine osteosarcomas.

Animals↗