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Biomedical subjects

H Martin

Publications and source records attributed to H Martin.

At least 613 records · Page 34Linked to original sources
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Post-translationally modified 14-3-3 isoforms and inhibition of protein kinase C.

This report compares the ability of individual members of the 14-3-3 protein family to inhibit particular protein kinase C (PKC) isoforms. We also show that two of these 14-3-3 isoforms (alpha and delta) specific to mammalian and avian brain are in vivo post-translationally modified forms of beta and zeta respectively. The presence of this modification enhances the activity of 14-3-3 as an inhibitor of protein kinase C nearly two fold. A method for analysing isoforms of 14-3-3 on acid-urea gels is also described. This permits the complete separation of all major isoforms and their unequivocal identification by a range of isoform specific antisera. The activity of recombinant 14-3-3 and isoforms renatured by a novel method after separation by reverse phase HPLC are compared. The effects of diacylglycerol and the phorbol ester, PMA (phorbol 1 2-myristate 13 acetate) on the inhibition suggest that one of the sites of interaction of 14-3-3 may be the cysteine-rich (C1) domain in PKC.

14-3-3 Proteins↗
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Comparison of toxicity and outcome in patients with acute myeloid leukemia treated with high-dose cytosine arabinoside consolidation after induction with a regimen containing idarubicin or daunorubicin.

The toxicity and outcome after high-dose ara-C/daunorubicin (HDara-C/DNR) consolidation therapy in de novo AML was compared in 11 patients who received an idarubicin-containing induction therapy (IDA; from June 1995 to March 1997) and 16 patients pretreated with daunorubicin (DNR; from July 1990 to May 1995) for induction. The DNR group consisted of two cohorts, one (n = 6) of patients who had received, as had the IDA group, two induction and one intermediate-dose ara-C consolidation courses, and another (n = 10) of patients who had been pretreated with one induction and one consolidation course prior to HDara-C/DNR. There was no difference in the relative dose between the three cohorts. Following HDara-C/DNR, the IDA-pretreated patients experienced a more prolonged myelosuppression during consolidation therapy compared with the DNR group. Duration of neutropenia (< 500 neutrophils/microl) following HDara-C/DNR was 31.2 +/- 16 days (mean +/- SEM) in the IDA group compared with 18.7 +/- 5 days in the DNR group (p < .001 Mann-Whitney U-test). The duration 'of thrombocytopenia (platelets < 25000/microl) was 34.8 +/- 20 days in the IDA group vs. 18.5 +/- 6 days in the DNR group (p < .005). The more prolonged myelosupression was associated with a longer duration of fever (18.9 +/- 24 vs. 6.9 +/- 5.2 days). A greater incidence, length (11 +/- 8 vs. 1.2 +/- 2 days), and severity of diarrhea were observed in the IDA-pretreated group. Three of 11 IDA patients experienced WHO grade III-IV diarrhea. In the IDA group two patients developed severe enterocolitis with Candida septicemia, and one of these patients died. One patient in the IDA group died during prolonged aplasia. In the DNR group 6/16 patients experienced grade I-II diarrhea. Two patients in each group died during consolidation therapy. The CR rate was 87% in the IDA group and 79% in the DNR group. Relapse-free survival after HDara-C is 50% at a median follow-up of 60 months in the DNR group and 45% after a median follow-up of 17 months in the IDA group. Whether the advantage of the superior response rate in the IDA-treated patients may be lost during HDara-C consolidation treatment due to increased toxicity remains to be proven in larger trials.

Acute Disease↗
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Peptide immunocytochemistry in afferent neurons from lower gut in rats.

Several peptides were detected in primary sensory neurons located in nodose and dorsal root ganglia and projecting from rat cecum and rectosigmoid, through a combination of retrograde staining by the fluorescent tracer DY-2HCl and of the immunofluorescent procedure of Coons. The three larger cell populations thus identified stored immunoreactive components respectively similar to calcitonin gene-related peptide (CGRP), substance P (SP), and a peptide related to peptide histidine methionine (PHM). The later immunoreactivity consisted of a single molecular form with an apparent molecular weight smaller than PHM itself. Fewer cells contained components immunologically similar to somatostatin 14 (ST14), to the 1-14 N-terminal sequence of somatostatin 28 (1-14 S28), and to neuropeptide Y (NPY). Neonatal treatment with capsaicin resulted in a drastic reduction of immunoreactivity for SP, PHM, ST14, 1-14 S28, and in a partial reduction of CGRP-like positive perikarya. These results demonstrate that several peptides are potentially involved in the sensory innervation of the lower gut in rat.

Afferent Pathways↗
PubMedDate not supplied

Ex vivo expansion of highly purified NK cells for immunotherapy after haploidentical stem cell transplantation in children.

BACKGROUND: Allogeneic natural killer (NK) cells are known to show medium to high cytotoxic activity against HLA-nonidentical leukemia or tumor cells. For a possible benefit of post transplant treatment with NK cells after haploidentical stem cell transplantation (haplo-SCT) we developed a clinical scale procedure for NK cell processing observing Good Manufacturing Practice (GMP). METHODS: Allogeneic donor NK cells were selected from 15 unstimulated leukaphereses using two rounds of immunomagnetic T cell depletion, followed by an NK cell enrichment step. CD56 (+)CD3 (-) NK cells were stimulated and expanded in vitro according to GMP. Quality control of NK cell purity, residual T cells and cytotoxic activity was done by multi-coloured flow cytometric analyses. RESULTS: Purification led to an absolute number of 234-1 237 x 10 (6) CD56 (+)CD3 (-) NK cells from leukapheresis harvests with a median purity of 95 % and a 4 to 6(1/2) log depletion of T cells. After two weeks stimulation with IL-2 a five-fold expansion of NK cells with a T cell contamination below 0.1 % was reached. Median cell viability was 95 % after purification and 99 % after expansion. The IL-2 stimulated NK cells showed a highly increased lytic activity against the MHC-I deficient K562 cells compared to freshly isolated NK cells and a medium cytotoxicity against patients' leukemic cells. CONCLUSIONS: Clinical scale enrichment and activation of allogeneic donor NK cells is feasible. High dose NK cell application may be a new treatment option for pediatric patients with leukemia or solid tumors in case of minimal residual disease or unbalanced chimerism post haplo-SCT as we could show for the first three patients .

Antigens, CD19↗
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Thallium elimination kinetics in acute thallotoxicosis.

This is a presentation of an acute fatal case of thallotoxicosis. The symptomatology of this ingestion and the absorption, distribution, and excretion of thallium will be discussed. Reliable pharmacokinetic information, monitoring the disappearance of thallium, will be correlated to the clinical events. This paper makes a contribution to the toxicology of thallotoxicosis in terms of kinetics of thallium and pharmacokinetics in acute ingestion. Values obtained on multiple, sequential, whole blood concentration, urine, fecal and bile contents, and eventually coronary sinus blood and organ analysis obtained at necropsy of brain, kidney, liver, and lungs and residual material obtained from the ileum and colon, are reported. The kinetics of elimination were determined from the values previously mentioned. Prussian Blue was found to be ineffective in preserving life in this case, although increased urine and fecal excretion of thallium occurred with its use. Kayexalate did not appear to contribute to the therapy in this case. Earlier and more aggressive treatment is recommended. Kinetic events in relation to neurological effects, as well as other signs and symptoms, are discussed. The histological necropsy findings from this fatal ingestion will also be presented. Recommendations in clinical, toxicological, and therapeutic areas are made.

Adult↗
PubMedDate not supplied

Mothers' play with toys: a longitudinal study with Down's syndrome infants.

Play with parents is recognized as an important learning medium for all children, yet there have been remarkably few studies of mothers' spontaneous actions with toys while playing with their children and none at all with Down's syndrome infants. This was a home-based study which commenced when the infants were 12 months old, and observations were made at approximately 6-weekly intervals until the infants were 24 months old. Significant differences were noted in mothers' play patterns with different toys and over the year there were marked changes in their actions. These seemed to result from developments in the children's play with toys. The findings reinforce the competency of most mothers as interactors with, and teachers of, their children. Possible implications for intervention strategies are discussed, especially the provision of more specific information about the sequences of development in children's play.

Adult↗
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Feedback.

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Female↗
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Future shock.

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Aged↗
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[Age-dependent changes in glucocorticoid receptors in rat liver following functional loading in in-vivo and in-vitro systems].

In aging the transformation, nuclei binding, and recycling of glucocorticoid receptor complexes (GRC) seem to be retarded or disturbed, as shown in the rat liver after stress and in an in vitro-system. Reasons of the retarded in vitro-transformation and DNA-binding could be changed properties of the receptor protein or of cytosolic modulators, in which the tested heat-stable factor f is not responsible for the aging changes. The observed aging differences, when studying the nuclei binding after Ca2+ addition, result in the question, to what extent phosphorylation/dephosphorylation processes play a role in transformation and nuclei binding of GRC.

Aging↗
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[Animals as models in experimental gerontology--comparative aspects].

In experimental gerontology animal models are of fundamental importance in further development of knowledge. The comparison between different models and between model and conditions in man depends on the individual position in the hierarchy of phylogenetic evolution and the examined process. In comparison with man short lived mammals are the most useful models. Nevertheless the comparison with more distant classes and species offers an additional insight and a more critical consideration of basic processes and of hypotheses of ageing in the general understanding of biological ageing.

Aging↗