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Biomedical subjects

M Kessler

Publications and source records attributed to M Kessler.

At least 19 recordsLinked to original sources

[Polycythemia after kidney transplantation].

Between 1971 and 1990, 251 kidney transplanted patients with a well functioning graft were evaluated to determine the frequency of post-transplant erythrocytosis (PTE). Thirty-one patients (13 percent) developed polycythaemia 10.6 +/- 10 months after transplantation. Thromboembolic complications occurred in 22 percent of the cases. The frequency of PTE was higher in males than in females (sex ratio: 7.2 vs 2.1; P < 0.05). Patients with renal dysplasia had a lower incidence of PTE (3 vs 22 percent; P < 0.05) as did those who had been treated with azathioprine (9.4 vs 19 percent; P < 0.05). None of the patients treated with recombinant erythropoietin before transplantation developed PTE during a mean follow-up of 15.1 +/- 4.5 months. The majority of polycythaemic patients had normal erythropoietin levels. These results show that there is an erythropoietin-independent proliferation due to an increased sensitivity of erythroid progenitors or to an erythroid stem cell stimulation by cytokines.

Adult

Parameters affecting the elongation block by RNA polymerase II at the SV40 attenuator 1 in vitro.

We have previously suggested that folding of the SV40 attenuator RNA 1 into two hairpin elements leads to a block of transcription elongation. Using site-directed mutagenesis, we created three templates that either strengthened or weakened the proposed hairpin structures. The mutated and wild-type templates were cloned downstream from the adenovirus 2 MLP, and transcription patterns were compared among the templates, in cell-free extracts. In this report, we show that at the standard temperature (30 degrees C) the elongation block occurs at elevated KCl concentrations (0.5-1.2 M KCl) while at high temperature (65 degrees C), although the transcription elongation rate increases, the block to elongation occurs at lower KCl concentrations (less than 0.5 M KCl) as well. Since under the conditions tested the extent of the elongation block is directly dependent on the stability of the hairpin structure of the RNA, as assessed by a comparison of transcription of the wild-type and mutated templates, we suggest that elevated KCl concentrations and high temperatures are favored conditions for optimizing the processes whereby the hairpin structures are recognized by the polymerase as an attenuation signal. Moreover, the present experiments indicate that cellular elongation factors are not directly involved in modulating the extent of the elongation block at the SV40 attenuator 1 in vitro. The SV40 attenuator 1 is the only eukaryotic system known to date which has been shown to have structural characteristics so similar to rho-independent terminator in prokaryotes. We discuss the similarities between the mechanisms which lead to elongation blocks at these eukaryotic and prokaryotic sites.

Base Sequence

Stochastic progression of new states in psychotherapy.

This paper presents a study of the stochastic behaviour of the entry of a 5-dimensional, 2400 state, system into new states. Each state consists of five measurements on variables that are sensitive measures of the degree of activated unconscious communication. The data come from six psychotherapy consultation sessions. The study sought to investigate the manner in which patient and therapist progress into new configurations (new states) of the five variables, and the way tension accumulates to the point of overcoming the inertia in the patient/therapist system. We show that the time series that consists of the time intervals between successive new states is a generalized Poisson process. That is, the process is inherently governed by a Poisson parameter that is a continuous piecewise linear function of time. It increases rapidly in the opening moments of an interview and decreases slowly thereafter. This non-linear, non-stationary Markov model fits the data well according to the Kolmogorov-Smirnoff criterion. We discuss the model's implications for the nature of psychotherapy and its participants.

Communication

Monitoring of redox-state of respiratory enzymes and myoglobin oxygenation in the working rat heart in normoxia and oxygen deficiency.

The cellular oxygen supply in the isolated, hemoglobin-free perfused, working rat heart can be determined by measurements of myoglobin oxygenation. However, for a precise analysis of mitochondrial hypoxia and anoxia (pO2 < 0.01 Torr) redox-state of respiratory enzymes must be known. By use of the EMPHO (Frank et al. 1989) it is possible to perform a high speed spectrometry within very small tissue volumes. Because of the characteristic absorption spectra of oxygenated and deoxygenated myoglobin and of the oxidized and reduced cytochrome aa3 within the wavelength interval from 500 to 630 nm it is possible to isolate these two pigments from the remission spectra and to determine the oxygenation state of myoglobin and the redox-state of cytochrom aa3.

Animals

Dialysis-associated arthropathy: a multicentre survey of 171 patients receiving haemodialysis for over 10 years. The Co-operative Group on Dialysis-associated Arthropathy.

In order to determine the prevalence of dialysis-associated arthropathy (DAA) and what factors favour its development, we conducted a survey in 19 centres in northeastern France, of all patients receiving haemodialysis for over 10 years (171). A diagnosis of DAA was made in 84 patients (49%) by two investigators, using as criteria single or combined presence of carpal tunnel syndrome (32%), erosions and bone cysts of the large limb joints (33%) and destructive spondylarthropathy (14%). The 84 patients with DAA were compared with the 87 dialysis patients free of these clinical or radiological abnormalities. The affected patients were significantly older at the start of dialysis than unaffected patients. The risk of developing carpal tunnel syndrome increased with the duration of dialysis. Amyloid deposits were found in carpal tunnel tissue obtained from 24 of the 39 operated patients (62%) during surgery. Destructive spondylarthropathy was significantly associated with the presence of disc calcifications and more frequent in AN 69-treated patients in whom secondary hyperparathyroidism appeared to be more severe. The use of an AN 69 membrane for at least 90% of the dialysis period (in 15 patients) was not associated with a lower prevalence of DAA. We found that after 10 years of haemodialysis DAA occurred whatever type of membrane was used and the prevalence increased with the patient's age and the duration of dialysis.

Adolescent

Evidence that high- and low-affinity DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding sites reflect membrane-dependent states of a single receptor.

Binding of DL-alpha-[3H]amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ([3H]AMPA) to lysed rat brain membranes in the presence of potassium thiocyanate resulted in curvilinear Scatchard plots that could be resolved by regression analysis into a large low-affinity component and a small high-affinity component. Solubilization with Triton X-100 resulted in solubilized and nonsolubilized fractions that were considerably enriched in the high-affinity component and correspondingly reduced in the low-affinity component. It thus appears that solubilization converts low-affinity AMPA receptors into high-affinity receptors. Also, synaptic plasma membranes were found to be greatly enriched in the low-affinity form and deficient in the high-affinity form of the AMPA receptor. These experiments provide evidence for the hypothesis that the high- and low-affinity components of AMPA binding are interconvertible states of the same receptor rather than separate binding sites and that the conversion of these receptors from their native high-affinity state to the low-affinity state occurs on insertion of the receptors into synapses.

Animals

Functional reconstitution of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors from rat brain.

Glutamate receptors belonging to the subclass specifically activated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) were solubilized from rat forebrain membranes with Triton X-100 and partially purified through a series of three chromatographic steps. Specific [3H]AMPA binding increased 30-60-fold during the isolation procedure. A protein band recognized by antibodies against specific amino acid sequences of the glutamate receptor-A subunit was enriched with each purification step; the molecular mass of this band (105 kDa) corresponded to that of cloned AMPA receptor subunits. Photoaffinity labeling of forebrain membranes with 6-cyano-7-[3H]nitroquinoxaline-2,3-dione, a specific antagonist of the AMPA receptor, labeled a single band that comigrated with the immunolabeled protein. On reconstitution of the partially purified material into bilayer patches, single-channel current fluctuations were elicited by 300 nM AMPA and blocked by 1 microM 6,7-dinitroquinoxaline-2,3-dione.

Animals

Premature termination and processing of human immunodeficiency virus type 1-promoted transcripts.

We have used transient expression assays to study transcription directed by the human immunodeficiency virus (HIV) type 1 promoter. A plasmid containing an HIV-reporter gene fusion and a simian virus 40 origin of DNA replication was transfected into COS-1 cells in the presence or absence of a Tat expression vector. HIV-promoted RNA was analyzed by in vivo labeling, by RNase protection mapping, and in run-on transcription assays. As observed previously, two populations of HIV RNA accumulate in vivo: short, attenuated transcripts and long, polyadenylated mRNA. The short transcripts labeled in vivo were longer and more heterogeneous than expected from RNase protection assays. Moreover, comparison of transcripts labeled in vivo with run-on transcription products revealed that similar, if not identical, short RNAs accumulate in vitro. Utilizing the run-on assay, we show that following transcriptional termination, the attenuated transcripts undergo processing to generate one species of RNA. We also provide evidence that Tat does not act as an antiterminator to relieve a discrete elongation block but instead modifies transcriptional complexes, enabling them to overcome putative pause sites and continue transcription of the template.

Base Sequence

The interaction of heparin and basic fibroblast growth factor on collagen synthesis in 21-day fetal rat calvariae.

We examined the interactions of the glycosaminoglycan, heparin, and recombinant human basic fibroblast growth factor (bFGF) on collagen synthesis in 21-day fetal rat calvariae. In calvariae treated for 96 h, heparin (25 micrograms/ml) and bFGF (10(-9) M) inhibited collagenase-digestible protein (CDP) labeling by 52 and 60% of control, respectively, and the combination further inhibited CDP labeling. Inhibition of CDP labeling by heparin (25 micrograms/ml) or bFGF (10(-9), 10(-8) M) was similar in the presence or absence of aphidicolin (30 microM) an inhibitor of cell replication. Heparin selectively inhibited CDP labeling in the osteoblast rich central bone but bFGF alone or in combination with heparin inhibited CDP labeling both in the periosteum and central bone. Heparin and bFGF alone decreased steady state levels of alpha 1(I)procollagen messenger RNA (mRNA) at 24 h and the combination further decreased mRNA levels. A high concentration of insulin-like growth factor-1 (IGF-1, 3 x 10(-8) M) reversed the inhibitory effect of heparin on DNA synthesis and CDP labeling. In contrast, IGF-1 could not reverse the inhibitory effects of bFGF on CDP labeling but enhanced the stimulatory effects of bFGF on thymidine incorporation into DNA. We conclude that the inhibitory effects of heparin and bFGF on CDP are independent of effects on cell replication. We further conclude that both heparin and bFGF inhibit collagen synthesis at a pretranslational site since they decreased procollagen mRNA levels in osteoblasts. However, the inhibition of collagen synthesis by heparin and bFGF appears to involve divergent pathways since exogenous IGF-1 could overcome the effect of heparin but not bFGF on collagen synthesis.

Animals

Routine measurement of hydrostatic intraperitoneal pressure.

A simple, non-invasive and well-tolerated technique for routine measurement of intraperitoneal hydrostatic pressure (IPP) in patients treated with peritoneal dialysis (PD) is presented. The height of the dialysis fluid in the PD line was measured, under atmospheric pressure, before drainage and during inspiration (IPPinsp) and expiration (IPPexp), taking the axillary line as the reference point of the resting subject in strict supine position. Normal values were established for a population of 18 patients treated with PD for 19.8 +/- 20.9 months under clinical and biological stable conditions. For an intraperitoneal volume of 2,820 +/- 419 ml, IPPinsp = 14 +/- 2 cmH2O; IPPexp = 12 +/- 2 cmH2O; IPP mean (defined as (IPPinsp+IPPexp)/2) = 13 +/- 2 cmH2O; IPP (defined as IPPinsp - IPPexp) = 2 +/- 2 cmH2O. IPP could not predict mechanical complications (hernia, hemorrhoids, dialysis fluid leakage) but the maximal IPPexp clinically tolerated was 20 cmH2O.

Female