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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 793 records · Page 44Linked to original sources

Comparative pharmacokinetics of antitumor Vinca alkaloids: intravenous bolus injections of navelbine and related alkaloids to cancer patients and rats.

The kinetics of distribution and elimination in rats of the antitumor drug navelbine and of two of its analogues, Na-formyl navelbine and deacetyl navelbine amide, have been studied by radioimmunoassay and compared with the kinetics obtained with vinblastine and vincristine. Fitting to two-exponential curves was used to derive pharmacokinetic parameters. Clearance was found to parallel toxicity for all drugs: it increases from 0.19 1 h-1 kg-1 for vincristine to 0.41 for Na-formyl navelbine, 1.4 for vinblastine, 2.3 for navelbine, and 2.6 for deacetyl navelbine amide. Terminal half-lives were longer for the Na-formyl-substituted alkaloids (around 13 h) than for the others (8-10 h). We have also studied navelbine kinetics in cancer patients entered in recent navelbine clinical trials and found that navelbine pharmacokinetics are characterized by fast and extensive distribution, high clearance (0.92 +/- 0.27 1 h-1 kg-1), and a relatively long terminal half-life (31.2 +/- 4.4 h). Relationships between chemical structure, pharmacokinetic properties, and toxicity or therapeutic efficiency within the Vinca alkaloid series are discussed, together with the relevance of animal models such as the rat in the screening of new antitumor drugs.

Animals↗

Comparative studies on recognition of faces, mimic and gestures in adolescent and middle-aged schizophrenic patients.

In adolescent and middle-aged schizophrenic patients and normals 10 different multiple-choice tests of 12 scored movie scenes lasting 10s were applied, measuring the ability to recognize faces, persons and mimic expressions. In all tests errors were significantly higher by a factor of 7 to 14 in patients as compared to normals. The relative impairment of adolescent schizophrenic patients (as compared to adolescent normals) was somewhat stronger than that of adult schizophrenics. This supports the hypothesis that the impairment found in schizophrenic patients is caused by the disease and not by other factors such as duration of illness or hospitalization.

Adolescent↗

Interstitial radiation therapy for squamous cell carcinoma of the tonsillar region: the Creteil experience (1971-1981).

From July 1971 to December 1981, 33 selected patients with T1, T2 tumors of the tonsillar region were treated according to the following protocol: 1. Telecobalt therapy to the primary site and to neck nodes to a dose of 45 Gy. 2. Brachytherapy to the primary site to a dose of 30 Gy using iridium 192. 3. Boost dose to involved neck nodes with electrons, or radical neck dissection, whether N1, N2, or N3. The actuarial disease-free survival was 76% when all patient groups were included and 80% for the N0 patients. The local control rate was 100%. Disease control in the neck was 94% overall and 100% for the N0 group. These results favor the use of this protocol for superficial, minimally infiltrating tumors less than 4 cm in diameter, without obvious extension to the base of the tongue or retromolar trigone.

Adult↗

Interleukin 1 induces specific phosphorylation of a 41 kDa plasma membrane protein from the human tumor cell line K 562.

An in vitro system was established to investigate the early effects of interleukin 1 (IL 1) on a clearly defined subcellular system, the plasma membrane. Murine IL 1 was obtained from the macrophage tumor line P 388 D1 and purified to apparent homogeneity. Plasma membranes from the human leukaemic tumor cell line K 562 were highly purified by differential ultracentrifugation. The monokine induced the specific phosphorylation of a 41 kDa plasma membrane protein. This could be demonstrated by incubating the plasma membranes in the presence of IL 1 and (gamma-32P)-ATP, separating the proteins by SDS-PAGE and subsequent autoradiography. A first biochemical reaction caused by IL 1 in the target organelle of the cell, the plasma membrane, was discovered, yielding a clue of how signal transmission may take place finally resulting in the stimulation of the responding cell.

Cell Line↗

The receptor for interleukin 1 in plasma membranes of the human leukemia cell K 562: biological and biochemical characterization.

Murine interleukin 1 (IL 1) inhibited concentration dependently the proliferation of murine T cell lymphomas and the human leukemic cell line K 562. The cytostatic action of IL 1 was not associated with cytotoxicity and appeared to be irreversible. Changes in the expression of surface antigens, like a rapid decrease of transferrin receptors or, more delayed, an increase in HLA-A, B, C antigen density suggested that a differentiation step was induced by IL 1. This effect of IL 1 was a direct one and most likely mediated by a specific receptor molecule. In order to characterize the receptor for IL 1, highly purified plasma membranes from K 562 were incubated with murine IL 1, and the phosphorylation pattern of plasma membrane proteins was investigated by the addition of radiolabeled ATP. At 0 degree C, IL 1 induced the specific phosphorylation of a 41 kDa membrane protein in a time- and concentration-dependent manner. Analysis of the phosphoamino acid composition revealed that IL 1 induced specifically the phosphorylation of tyrosine residues of the 41 kDa protein. Crosslinking experiments proved that the 41 kDa protein had an IL 1 binding site, strongly suggesting that the 41 kDa protein was the receptor for IL 1 itself. Affinity labeling with an ATP-analogue showed that this protein possessed an ATP binding and cleaving site. We conclude from this that the receptor for IL 1 in the plasma membranes of K 562 is a transmembranous protein of 41 kDa, which possesses a tyrosine specific protein kinase activity with an autophosphorylating capacity.

Animals↗

Transconjunctival oxygen monitoring as a predictor of hypoxemia during helicopter transport.

As the use of helicopters for air transport of critically ill patients increases, the availability of monitoring devices for physiological parameters during flight becomes important. It has long been known that arterial PO2 (PaO2) decreases during unsupplemented, non-pressurized flight. In this study, the authors examined the use of the transconjunctival oxygen (cjO2) monitor for assessing the adequacy of arterial oxygenation during helicopter flight in four healthy volunteers. Arterial PaO2 as measured by conventional blood gas analysis was compared with cjO2 at ground level, 5,000 feet, and 10,000 feet altitude. Mean PaO2 dropped significantly from 93.5 to 81.5 to 58.5 mm Hg, respectively (P less than 0.001, analysis of variance with repeated measures). Mean cjO2 also decreased significantly from 63.8 to 52.0 to 34.8 mm Hg, respectively (P less than 0.001, analysis of variance with repeated measures). Within individual subjects, cjO2 was an accurate predictor of PaO2 (P less than 0.001, multiple regression analysis). The relationship between cjO2 and PaO2 was linear with a regression coefficient of 1.147. The authors conclude that the transconjunctival O2 monitor may be useful for monitoring the adequacy of arterial oxygenation during helicopter flight in hemodynamically stable patients. The results of study also support the use of supplemental oxygen in all patients subjected to helicopter transport.

Adult↗

In vitro growth potential of fibroblasts isolated from pigs with radiation-induced fibrosis.

Degenerative processes were studied in pig muscles irradiated with single doses of 30 or 40 Gy. Damaged muscle was gradually replaced by an invasive fibrotic tissue. As a control, surgical muscle exeresis was performed of the same size as the radiation-induced lesions at the same anatomical site. Primary cultures were set up comprising cells freshly extracted from normal dermis, or from tissue exhibiting either normal wound fibrosis or radiation-induced fibrosis. The growth potential of cells taken from the latter region far exceeded that of the two other types; attachment efficiency was higher, and fibronectin was detected early by immunofluorescence. These in vivo and in vitro observations imply that a pathological repair process occurs after localized irradiation.

Animals↗

Defining irrational action in medical and psychiatric contexts.

In their book Culver and Gert define irrational action in the context of medicine and psychiatry. This definition is used to define other key concepts including Malady. It is argued that their definition provides neither a necessary condition nor a sufficient condition for an action to be irrational in this context.

Humans↗

The catalytic mechanism of angiotensin converting enzyme and related zinc enzymes.

Angiotensin converting enzyme (ACE) is one of a class of zinc peptidases that utilize glutamic acid as a catalytic residue. ACE also has important arginine and tyrosine residues that are involved in substrate binding and a lysine that binds chloride. Chloride activation of ACE depends on the particular substrate employed. It is an essential activator of class I substrates and a nonessential activator of class II substrates. Radiationless energy transfer using substrates labeled with the fluorescent dansyl group indicates that chloride promotes a two-step binding process. The second step is a change in protein conformation that can be monitored using fluorescent inhibitors. The chloride binding constant for the ACE-inhibitor complex at pH 7.5 is 2.2 mM.

Animals↗