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Biomedical subjects

I Seres

Publications and source records attributed to I Seres.

29 records · Page 2Linked to original sources
PubMed1994

Age-related changes in signal transduction. Implications for neuronal transmission and potential for drug intervention.

Problems associated with aging will become one of the leading health dilemmas of the next century. Age-associated diseases, including those affecting the neuronal system, are increasing in frequency. Age-related deficiencies in the brain result in impaired motor functions, sleep, behaviour and cognitive functions. Good functioning of the brain is based on the communication between neurons, by means of signal sending and processing. Neuronal transmission is a very complex phenomenon which involves neuromediator receptors, ion channels and various signal transduction systems. Aging is associated with modification of many brain neurotransmitter and second messenger systems directly involved in signal transduction. Thus, signal transduction events that are deficient in the aged include calcium mobilisation, phosphatidylinositol breakdown, cyclic nucleotides formation, accumulation of proto-oncogene transcripts and synthesis of new proteins, such as certain neurotransmitters. Other events in signal transduction, such as protein tyrosine kinase activity, G-protein structure and function and receptor-G-protein coupling, have not been studied in great detail as yet. Alterations in these various intracellular signalling events may fundamentally influence the functional activity of neurons, and, in consequence, play an important role in the age-dependent alterations of brain functions. Future studies are needed to better understand the molecular basis and the importance of signal transduction changes with aging. Such knowledge will certainly lead to design of better drugs for the prevention or treatment of age-related deficiencies or diseases, such as Parkinson's disease or Alzheimer's disease.

Aging↗
PubMed1993

Age-dependent alterations of human recombinant GM-CSF effects on human granulocytes.

The granulocyte-macrophage colony stimulating factor (GM-CSF) is an important in vivo regulator of granulopoiesis and neutrophil functions. It is well-known that the immune response and the transmembrane signalling in immune cells change with aging. We wished to elucidate the effects of GM-CSF in itself and in priming the activities of other inflammatory agents on neutrophils of elderly persons. Neutrophils of 20 healthy elderly (aged 60-90 years) and 20 healthy young (aged 20-25 years) subjects were studied for superoxide anion production, intracellular free calcium mobilization, antibody dependent cellular cytotoxicity (ADCC) and intracellular killing activities. It was found that GM-CSF is unable to prime neutrophils of elderly subjects to the action of FMLP, metenkephalin or opsonized zymosan. By the use of Pertussis toxin and H7 it was demonstrated that a different signal transduction pathway in neutrophils of elderly subjects is activated by GM-CSF or FMLP if compared to that of young subjects. These results suggest that the lack of priming could contribute to the greater susceptibility of the elderly to infections and that the change of the signal transduction mechanism in neutrophils of elderly subjects might partly explain this phenomenon.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Age-dependent changes in transmembrane signalling: identification of G proteins in human lymphocytes and polymorphonuclear leukocytes.

In human neutrophils (PMNLs) we found that in the elderly IP3 formation was significantly decreased compared to that of young subjects. For FMLP receptor binding affinity and number no measurable differences occurred upon ageing, studying both the low or the high affinity receptors. The amount of ADP-ribosylated G proteins, catalysed by pertussis toxin (PT) or cholera toxin (CT), was significantly increased in PMNLs of the elderly. In lymphocytes, the PT-catalysed ADP ribosylation of G proteins was also increased with ageing, while the CT-catalysed ribosylation was decreased. The autoradiogram of [32P]ADP-ribosylated proteins by CT in lymphocytes of young individuals showed a major polypeptide of 40,000 M(r). In contrast, in lymphocytes of the elderly, the major polypeptide was 45,000 M(r). In PMNLs, CT labelled quite strongly the 45,000 M(r) band, mainly in the elderly. When PT was used, no age-related pattern changes could be demonstrated, while differences could be observed between the two types of cells. The use of antiserum P680 (G alpha common) showed no age-related pattern changes, while the intensity of the labelled proteins varies with age and cell type. The antiserum U46 (Go alpha) could identify in lymphocytes of young subjects two polypeptides 68,000 and 41,000 M(r). The prominent polypeptide in lymphocytes of the elderly was the 70,000 M(r) and no other polypeptides could be recognized. In PMNLs of young subjects the U46 and serum identified a range of species. In PMNLs of the elderly all these bands were weakly labelled. The present data indicate changes in the pattern and the quantity of G proteins in lymphocytes and PMNLs of elderly subjects.

Adenosine Diphosphate Ribose↗
PubMed1992

Transmembrane signaling changes with aging.

Altered immune response and transmembrane signaling with aging has previously been demonstrated. The aim of the present study was to characterize PMNLs and lymphocyte G proteins and to determine whether their relative amounts are altered with aging. First we studied the effects of FMLP on PMNLs IP3 formation. It was found that in any group of elderly the PMNLs IP3 formation was significantly decreased compared to that of young subjects. In FMLP receptor binding affinity no measurable difference exists in either low- or high-affinity FMLP receptors. The autoradiogram of 32P-ADP-ribosylated proteins by CT in lymphocytes of young individuals showed a major polypeptide of 40 kDa, and two much less prevalent components of 52 and 45 kDa. In contrast, in lymphocytes of elderly subjects the major polypeptide was 45 kDa, and the two others were very weakly labeled. In PMNLs, CT labeled the 45-kDa band quite strongly, mainly in the elderly, and the 52- and 40-kDa bands were very weakly labeled, mainly in young subjects. When PT was used, no age-related pattern changes could be demonstrated, while differences could be observed between the two types of cells.

Adenosine Diphosphate Ribose↗
PubMed1992

Superoxide anion production and intracellular free calcium levels in resting and stimulated polymorphonuclear leukocytes obtained from healthy and arteriosclerotic subjects of various ages.

It has been established that phagocytic cells are integral components of advanced arteriosclerotic plaques but their role in plaque formation remains unclear. Therefore, toxic agents, such as superoxide anion produced by polymorphonuclear leukocytes (PMNLs) were studied in a clinically defined group of arteriosclerotic patients suffering from obliterative arteriosclerosis of the lower legs. Owing to a close correlation between O2- generation and calcium, the intracellular free calcium concentrations of PMNLs were measured in a resting state and after stimulation with various agents, for example, opsonized zymosan (OZ), the chemotactic peptide f-met-leu-phe (FMLP), and the calcium ionophore A23187. Healthy aged-matched controls were employed. The patients were divided into two age groups: 30-59 years and 60-80 years. We found that in the younger group of arteriosclerotic patients, superoxide anion production and intracellular free calcium concentrations were increased even in the resting state, and only a slight increase was observed after stimulation compared with healthy controls. Granulocyte responses seemed to be similar, independent of the patient's age, to those found in healthy elderly subjects. Arteriosclerosis appears to be associated with an early aging process expressing marked alterations that are greater than those associated with normal aging.

Adult↗
PubMed1992

[The accidents and complications of laparoscopy. A review of 8,915 cases].

Complications occurring in 8,915 laparoscopies done during 1957-1991 are analyzed. Complications were classified as major or minor, according to the need of surgical intervention for their management, and also in relation to pneumoperitoneum, introduction of the laparoscope, during the examination or after laparoscopy. The total number of major accidents was 54 (0.60%). Half of them as a consequence of the instrumentation or of liver biopsy. There were 442 minor complications (4.96%). Mortality included 10 patients (0.11%) as a sequel of uncontrolled haemorrhage, 5 of them after liver biopsy. The complications of laparoscopy cannot be ignored; as all invasive techniques it may have a risk, even in the most expert hands. Half of the major accidents and of the mortality were due to complications from liver biopsy.

Accidents↗
PubMed1988

Low C3 in cirrhotic ascites predisposes to spontaneous bacterial peritonitis.

The risk of developing spontaneous bacterial peritonitis (SBP) in relation to the concentration of C3 in ascitic fluid (AF) has been studied prospectively in 33 patients with cirrhosis of the liver, seven of whom had one or more episodes of SBP during hospitalization. C3 concentrations in the AF of patients who developed infection (9.0 +/- 2.67 mg/dl) were significantly lower than in those who did not (18.26 +/- 8.11 mg/dl) (P less than 0.01). C4 concentrations were similar in both groups. A direct correlation was found between AF C3 and total protein concentrations (P less than 0.001). We conclude that a low C3 concentration in AF may predispose to SBP.

Aged↗
PubMed1986

Effect of sulindac on prostaglandin excretion and renal function in cirrhotic patients with ascites.

The effect of sulindac, a nonsteroidal anti-inflammatory drug, on renal prostaglandin synthesis and renal function variables was investigated in six cirrhotic patients with tense ascites and marked sodium retention. We studied serum thromboxane (TXB2) production, urinary prostaglandin excretion (6-keto-prostaglandin F1 alpha and TXB2) and renal function before and after administration of a therapeutic dose of sulindac (400 mg). After treatment, no significant changes were observed in urinary prostaglandin excretion, serum creatinine concentration, urine volume, or urinary sodium and creatinine clearance, whereas the serum TXB2 concentration was reduced in 89%. In five patients systemic prostaglandins were inhibited, but renal excretion remained unchallenged. However, one patient showed marked reduction of urinary prostaglandins associated with a depression of renal function. The study suggests that sulindac could be a safe substitute for other nonsteroidal anti-inflammatory drugs in cirrhotic patients with ascites. Further pharmacological trials seem to be warranted.

Ascites↗
PubMed1985

A double-quenching method for studying protein dynamics: separation of the fluorescence quenching parameters characteristic of solvent-exposed and solvent-masked fluorophors.

A novel experimental method, suitable for separate analysis of the quenching parameters characteristic of solvent-exposed and solvent-masked fluorophors of macromolecules, is described. The method is based on the modified Stern-Volmer analysis and requires simultaneous application of two kinds of quencher: one that can selectively quench the emission of exposed fluorophors (e.g., ionic quenchers) and another that is nonselective (e.g., oxygen or, in many cases, acrylamide), capable of quenching the fluorescence of both exposed and masked groups. In order to examine the accuracy of the model, a computer simulation was performed. The results showed that the errors are comparable to those arising from the conventional quenching experiments. The method is applicable to phosphorescence quenching as well and is extendable to time-resolved measurements (by replacing fluorescence intensities with lifetimes). The method was applied to resolve the quenching parameters of lysozyme fluorescence by the use of iodide as selective and acrylamide as nonselective quenchers. The determination of the acrylamide quenching constant associated with the internal fluorophor, Trp-108 (Kq = 3.5 M-1), permits specific studies on the dynamics of internal regions of the protein. The quenching constant determined for the more exposed residue Trp-62 (Kq = 1.6 M-1) provides local information about the surface independent of the electrostatic effects observed when an ionic quencher is used.

Animals↗
PubMed1984

Dynamic interaction between functional groups in the active site of glycogen phosphorylase b.

The quenching of coenzyme fluorescence in glycogen phosphorylase b is reinvestigated. Data with anionic quenchers show deviations from the original Stern-Volmer kinetics. A kinetic analysis based on measured lifetime data indicates a collisional quenching process, which is, however, not diffusion-controlled. It is proposed, that the quenching takes place primarily by enzyme-bound quencher species. The observed inhibition of the enzyme reaction by I- and IO-3 is consistent with this hypothesis. The inhibition pattern and spectral investigation refer to a true competition with the substrate, glucose-1-phosphate. So, this dynamic quenching can be regarded as an indicator of rapid conformational fluctuations which bring the two important active-site groups in contact. Effect of ligand binding on the quenching of coenzyme fluorescence should also be revaluated according to these results.

Animals↗