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Biomedical subjects

P Gross

Publications and source records attributed to P Gross.

At least 55 records · Page 3Linked to original sources
PubMed1999

Impact of the endothelin system on water and sodium excretion in patients with liver cirrhosis.

BACKGROUND: Impaired renal function in patients with liver cirrhosis is a serious complication and is characterized by sodium and water retention in the absence of identifiable specific causes of renal dysfunction. The endothelin system has been shown to be activated in liver cirrhosis and might contribute to impaired renal function. However, the mechanisms leading to an activation of the endothelin system in these patients and the effects of an activated endothelin system on renal function in these patients are as yet unknown. METHODS: To determine the correlation between the activity of the endothelin system and the ability to excrete water and sodium in patients with liver cirrhosis, we measured plasma endothelin-1 concentrations by reversed phase-HPLC followed by an endothelin RIA and performed an oral water load tests in 10 healthy control subjects and 43 patients with liver cirrhosis. In addition, we analysed possible mechanisms/factors like plasma endotoxin that might contribute to the activation of the endothelin system in liver cirrhosis. RESULTS: This study showed that the endothelin system is activated in patients with liver cirrhosis in a disease-stage-dependent manner. Patients with Child C liver cirrhosis have a 5.45-fold increased plasma ET-1 concentration compared to healthy controls, whereas plasma ET-1 is only increased 2.74-fold in Child A patients. An oral water load test revealed a highly significant (P < 0.0001) inverse correlation between the plasma endothelin-1 concentrations and the ability to excrete a given water load. Plasma endotoxin, a well-known stimulus of ET-1, is significantly (P < 0.03) correlated with plasma ET-1 in cirrhotic patients. The ET-1 concentrations in the ascites of patients with liver cirrhosis were lower and not related to plasma ET-1. CONCLUSION: The activity of the endothelin system in patients with liver cirrhosis depends on the severity of liver impairment. Plasma endotoxin might be an important stimulus of the endothelin system in liver cirrhosis. We observed a highly significant inverse correlation between the plasma endothelin-1 concentrations and the ability to excrete a given water and sodium load, suggesting that the endothelin system plays a role in the regulation of water excretion in patients with liver cirrhosis.

Case-Control Studies↗
PubMed1998

Quantitative hydroxyl radical footprinting reveals cooperative interactions between DNA-binding subdomains of PU.1 and IRF4.

Quantitative hydroxyl radical footprinting and fluorescence polarization measurements have been used to determine the dissociation constants (Kd) of complexes between the ets domain of the murine transcription factor PU.1 and three different DNA fragments. Two natural PU.1 binding sites, the SV40 enhancer site and the lambdaB motif of Iglambda2-4 enhancer, were used as well as the PU.1 binding site present in the crystallized PU.1-DNA complex. With the use of quantitative hydroxyl radical footprinting we obtained binding isotherms for individual protected nucleotides and contact sites on both strands of the DNA. Kd values of (1.53 +/- 0. 12) x 10(-)8 M were found for the lambdaB element, (3.60 +/- 0.65) x 10(-)8 M for the SV40 enhancer site, and (2.28 +/- 0.27) x 10(-)8 M for the sequence used in the crystal structure. In addition, the binding of a second protein, the DNA binding domain of IRF4, to the lambdaB site by itself and in the presence of PU.1 was analyzed. The IRF4 DBD shows three footprints on the TTCC strand and one footprint on the GGAA strand of the lambdaB element. The dissociation constant for the binary IRF4 DBD-lambdaB complex equals (5.59 +/- 0.60) x 10(-)7 M. The Kd value of the IRF4-lambdaB interaction is reduced by a factor of 5 in the presence of two different DNA-bound PU.1 protein constructs, PU.1 DBD and a PU.1 construct containing the PEST domain (PU.1-PEST). A similar decrease of the Kd value was observed for the binding of PU.1-PEST in the presence of DNA-bound IRF4 DBD demonstrating a cooperative interaction between the PU. 1-PEST and IRF4 DBD. On the basis of the hydroxyl radical footprints in the ternary PU.1/IRF4/lambdaB complex, a model for the interactions between the two proteins and the lambdaB site was developed. The DNA binding domains of both proteins bind the DNA in the major groove with potential protein-protein interactions near the intervening minor groove.

Animals↗
PubMed1998

Hydroxyl radical footprinting of DNA complexes of the ets domain of PU.1 and its comparison to the crystal structure.

Hydroxyl radical footprinting has been used to probe interactions in complexes between the ets domain of the murine transcription factor PU.1 and three different DNA restriction fragments, each containing one copy of the recognition sequence 5'-GGAA-3'. Two natural PU.1 binding sites, the SV40 enhancer site and the lambdaB motif of Ig lambda2-4 enhancer, were used as well as the PU.1 binding site present in the crystallized PU.1-DNA complex [Kodandapani, R., Pio, F., Ni, C.-Z., Piccialli, G., Klemsz, M., McKercher, S. R., Maki, R. A., and Ely, K. R. (1996) Nature 380, 456-460]. The footprints obtained for the three different DNA sequences are almost identical. The extent of contact with the protein was monitored for every base in the complex. Two concentration-dependent cleavage sites on the complementary TTCC strand are evidence of a specific interaction between PU.1 and the DNA. Two more protection sites and a hypersensitive cleavage site on the GGAA strand were observed. Although these data confirm the global structure of the PU.1-DNA complex as suggested by crystallography, the footprinting data reveal differences between the protein-DNA contacts in solution and in the crystal state. An additional interaction site not present in the crystal structure was observed by hydroxyl radical footprinting.

Animals↗
PubMed1998

Cytokine production after influenza vaccination in a healthy elderly population.

Influenza vaccination is less efficacious in the elderly than in the young. To characterize this age-related decrease in immune response to influenza vaccination, antibody and cell-mediated responses to influenza vaccine were assessed before immunization and 4 weeks after vaccination of a population of 270 healthy elderly individuals (mean age: 80.2 years) living in eight local continuing care retirement communities (CCRCs) and 30 young individuals (mean age: 27.8 years). The antibody titres produced against all three influenza strains increased significantly after vaccination in both the young and elderly (p < 0.0005); however, the young demonstrated significantly higher titres to all three strains than did the elderly (p < 0.03). Peripheral blood mononuclear cells (PBMC) cultured with influenza vaccine demonstrated significantly increased proliferation (elderly: p < 0.00005; young: p < 0.001) after vaccination, with proliferative responses in the young significantly higher than the elderly both before (p < 0.04) and after (p < 0.0005) vaccination. Similarly, IFN gamma production in these PBMC cultures increased significantly pre- to postvaccination in both young and elderly (young: p < 0.006; elderly: p < 0.00005), but the young produced more than the elderly both pre- and postvaccination (p < 0.0001). Following vaccination, PBMC production of IL-10 was higher in the young than in the elderly (p < 0.0015), while IL-6 production was comparable in both young and elderly individuals. Greater than 13% of the elderly population did not produce detectable IL-6, IL-10, or IFN gamma either before or after vaccination. The data show that the decreased cell-mediated and humoral responses to influenza vaccination of this healthy elderly population are accompanied by the production of lower levels of cytokines. A unique finding in this population of 270 healthy elderly was the association between a TH0 cytokine profile and intact immune responses to influenza vaccine. A similar relationship was not seen in the young.

Adult↗
PubMed1998

The treatment of severe hyponatremia.

Severe hyponatremia may be chronic (days) or acute (hours), symptomatic or asymptomatic. Severe chronic symptomatic hyponatremia (serum sodium concentration < 110 to 115 mM/liter) occurs most commonly in the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The treatment of this hyponatremia is a challenge to practicing physicians, in part because an overly rapid correction of hyponatremia may cause brain damage. The latter sometimes takes the form of central pontine myelinolysis (CPM). On the basis of available clinical and experimental literature, the rate of correction of this symptomatic hyponatremia should be no more than 0.5 mM per liter per hour, and the initial treatment should be halted once a mildly hyponatremic range of the serum sodium concentration has been reached (approximately 125 to 130 mM/liter). In contrast, severe chronic asymptomatic hyponatremia may be treated sufficiently by a fluid restriction. On the other hand, severe symptomatic acute hyponatremia should be treated promptly and rapidly, using hypertonic saline, to initially reach a mildly hyponatremic level.

Adolescent↗
PubMed1998

Severe hyponatremia after transsphenoidal surgery for pituitary adenomas.

Severe hyponatremia has been described after elective surgery with subsequent permanent brain damage. Other authors, however, have noted that morbidity and mortality rates of severe hyponatremia have been greatly overestimated. We retrospectively examined 19 patients (8 male, 11 female) who developed severe hyponatremia (100 to 124 mmol/liter) after transsphenoidal surgery for pituitary adenomas. Eight patients had hormonally inactive adenomas, 5 ACTH-secreting adenomas, 2 GH-secreting adenomas and 4 prolactin-secreting adenomas. The mean age of the patients was 47.5 years, with a range from 16 to 71 years. The mean preoperative serum sodium level was 137.8 mmol/liter. The timing of hyponatremia showed two different patterns. Five patients developed early postoperative hyponatremia (mean 114.0 mmol/liter +/- 4.85) and 14 patients showed the lowest mean serum level one week after surgery (118.1 mmol/liter +/- 6.86). Patients with early hyponatremia had fewer and less severe symptoms than patients with delayed hyponatremia. None of the patients developed seizures or a demyelination syndrome. Despite severe degree of hyponatremia for most of our patients treatment with water restriction and oral sodium supplementation was sufficient.

Adenoma↗
PubMed1997

[Aquaretic drugs--a new therapeutic principle in treatment of hyponatremia?].

The antidiuretic hormone (vasopressin) is involved, either directly or indirectly, in the pathogenesis of almost all forms of hyponatremia. This means that blockage of the ADH effect at the renal ADH receptor represents a rational approach in the treatment of hyponatremia, in particular in difficult-to-treat and symptomatic forms. Recently, orally absorbable, non-peptidergic competitive ADH antagonists (aquaretics) have been introduced, which bind with high affinity to renal ADH receptor subtypes. Initial investigations in humans show that the substance is well tolerated. Numerous studies on patients with hyponatremia of varying genesis have since been started. It is to be expected that the availability of this new dass of substances will result in marked improvements in the treatment of acute and chronic forms of hyponatremia.

Antidiuretic Hormone Receptor Antagonists↗
PubMed1997

[Sports activity and risk of arthrosis].

Although the potential risk of exercise-induced osteoarthrosis (OA) of weight-bearing joints such as hip, knee and ankle is of great public health importance, very little is known about it. One reason for this lack of knowledge may be the multifactorial etiology of degenerative joint disease, rendering it difficult to quantify the effect of an isolated factor such as exercise and sport on OA. The present review summarizes the current state of knowledge. Recent epidemiologic studies consistently find a slight increase in the risk of OA of hip and knee in those exercising very heavily, which is more marked in ball games than in endurance disciplines. Several epidemiologic studies (including the methodologically best ones) have investigated the effect of jogging on OA risk. They find that extremely active runners may be exposed to increased risk of OA of hip and knee that should not be totally disregarded. On the other hand, regular jogging in middle age is likely to help maintain physical function. A typical finding is that in former athletes the radiologic signs of degenerative joint disease appear to correspond more to the hypertrophic type (with osteophytes and subchondral sclerosis) than the destructive type (with joint space narrowing). This observation raises the question of the prognostic value of the radiologic signs observed in heavy exercisers. Accordingly, taking into account animal experiments and occupational studies as well, a slight increase in the risk of OA of weight-bearing joints due to very frequent and heavy exercise over many years cannot be entirely ruled out. However, for the majority of (less active) exercisers, recreational physical activity seems neither to increase nor decrease the risk of OA to any marked extent.

Ankle Joint↗
PubMed1997

[Sudden hyponatremia with unconsciousness. Case report and brief overview of the syndrome of inadequate antidiuresis (SIAD or Schwartz-Bartter syndrome].

A sixty-six year old female was admitted to the hospital with an incomplete hemiparesis on the left side combined with a short episode of unconsciousness. According to her husband's account she had a seizure. Relevant laboratory measurements: plasma sodium concentration 113.9 mmol/l, plasma concentration of ADH 10.3 pg/ml, urine sodium concentration 44.4 mmol/l. The plasma concentrations of creatinine and urea were within normal limits. The working hypothesis was SIAD (syndrome of inappropriate antidiuresis) or Schwartz-Bartter-syndrome. The patient was treated immediately with water restriction (500-1000 ml/day), furosemide and i.v. replacement of urinary sodium losses by 3% NaCl. The analysis of cerebrospinal fluid showed pleocytosis and increased concentrations of immunoglobulins G and M. Serological diagnosis was positive for antigen of varicella-zoster virus. These observations were thought to be compatible with a diagnosis of SIAD in the setting of encephalitis. Under water restriction, infusion of 3% saline, treatment with loop diuretics and aciclovir (3 x 750 mg daily) the neurological function returned to normal within 2 days. A standard oral water load on the 14th hospital days showed a return to a normal water metabolism.

Acyclovir↗
PubMed1996

Colicin M is inactivated during import by its immunity protein.

Colicin M (Cma) displays a unique activity that interferes with murein and O-antigen biosynthesis through inhibition of lipid-carrier regeneration. Immunity is conferred by a specific immunity protein (Cmi) that inhibits the action of colicin M in the periplasm. The subcellular location of Cmi was determined by constructing hybrid proteins between Cmi and the TEM-beta-lactamase (BlaM), which confers resistance to ampicillin only when it is translocated across the cytoplasmic membrane with the aid of Cmi. The smallest Cmi'-BlaM hybrid that conferred resistance to 50 micrograms/ml ampicillin contained 19 amino acid residues of Cmi; cells expressing Cmi'-BlaM with only five N-terminal Cmi residues were ampicillin sensitive. These results support a model in which the hydrophobic sequence of Cmi comprising residues 3-23 serves to translocate residues 24-117 of Cmi into the periplasm and anchors Cmi to the cytoplasmic membrane. Residues 8-23 are integrated in the cytoplasmic membrane and are not involved in Cma recognition. This model was further tested by replacing residues 1-23 of Cmi by the hydrophobic amino acid sequence 1-42 of the penicillin binding protein 3 (PBP3). In vivo, PBP3'-'Cmi was as active as Cmi, demonstrating that translocation and anchoring of Cmi is not sequence-specific. Substitution of the 23 N-terminal residues of Cmi by the cleavable signal peptide of BlaM resulted in an active BlaM'-'Cmi hybrid protein. The immunity conferred by BlaM'-'Cmi was high, but not as high as that associated with Cmi and PBP3'-'Cmi, demonstrating that soluble Cmi lacking its membrane anchor is still active, but immobilization in the cytoplasmic membrane, the target site of Cma, increases its efficiency. Cmi delta 1-23 remained in the cytoplasm and conferred no immunity. We propose that the immunity protein inactivates colicin M in the periplasm before Cma can reach its target in the cytoplasmic membrane.

Amino Acid Sequence↗
PubMed1996

Adult immunizations.

New vaccines have been licensed for hepatitis A, varicella, and typhoid. This paper reviews these vaccines and their recommended uses in adults. Special attention is given to a new national policy establishing age 50 years as a time for review of preventive health measures with emphasis on evaluating risk factors that indicate a need for pneumococcal vaccine and the initiation of annual influenza immunization.

Adult↗