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Biomedical subjects

A Gross

Publications and source records attributed to A Gross.

At least 109 records · Page 6Linked to original sources
PubMed1996

Interactions between professional phagocytes and Brucella spp.

Induced pathogenicity in animals and humans differs considerably. This review is devoted to the relations between Brucella spp. and professional phagocytes, particularly macrophages and macrophagic cell lines in vitro. Although numerous studies have been reported, the type of ingestion by macrophages, the receptor involved, and the molecular mechanisms, are poorly understood. The ability of most Brucella species to actively inhibit their ingestion by neutrophils or macrophages has been proposed as an explanation for the poor rate of in vitro phagocytosis and in vivo alteration of the phagocytic cells. Oxidative burst plays a significant role in the antibacterial processes of phagocytic cells. The effects of whole or fractioned B. abortus on the ability of neutrophils to induce an oxidative burst in response to stimulation with opsonized zymosan particles were examined. Besides oxygen-based killing, the phagocytic cells have developed other types of defence, including hydrolytic enzymes and reactive halides. Inside the cell, the bacteria encounter new environmental conditions. Their survival is conditioned by an adaptation to this new situation. Pathogens that have acquired the ability to multiply within macrophages should synthesize products specifically interacting with the host cell defence system. Survival of intracellular pathogens is closely linked to the mechanisms of evasion from cellular defences. Brucellae stay in membrane bound vacuoles called phagosomes, but the exact nature and the maturation pathway of this compartment have not yet been understood. Macrophages play a central role in the evolution of brucellosis; this first interaction between the pathogens and the cell will determine the course of the disease. There are natural differences between brucellae species regarding macrophage response to the bacteria.

Animals↗
PubMed1996

Serum lipoprotein (a) concentrations in a population of 819 non-insulin-dependent diabetic patients.

Variations in serum Lp(a) concentrations were studied in a large population of non-insulin-dependent diabetic (NIDDM) patients in relation to long-term complications. Lp(a) concentrations were measured by immunonephelometry in 819 NIDDM subjects and compared with those of 128 controls. Correlations were investigated relative to plasma lipid and glycaemic parameters, body mass index (BMI) and macro- and microvascular complications. Mean absolute and relative variations of Lp(a) concentrations were studied in a subgroup of 245 patients over a one-year period. No significant differences were found between Lp(a) concentrations in NIDDM and control subjects. No relationship was evidenced with macrovascular and microvascular complications or glycaemic control. Mean relative Lp(a) variations were correlated with BMI and absolute and relative variations in triglyceridaemia. These results confirm the absence of any alterations of Lp(a) concentrations in a large cohort of NIDDM patients, either with or without micro- and macrovascular complications, but suggest a particular modulatory role for BMI and serum triglyceride variations.

Adult↗
PubMed1995

Autosomal-recessive neural crest syndrome with albinism, black lock, cell migration disorder of the neurocytes of the gut, and deafness: ABCD syndrome.

We report on a macrosomic newborn girl with albinism, a black lock at the right temporo-occipital region, and retinal depigmentation. Bilateral deafness was confirmed by brainstem auditory-evoked potentials. In addition, the infant had a severe defect of intestinal innervation. Biopsy showed aganglionosis of the large intestine, and total absence of neurocytes and nerve fibers in the small intestine, indicating a total lack of sympathetic and parasympathetic innervation. The infant died of intestinal dysfunction at 5 weeks. She was the 14th child of consanguineous Kurdish parents. Four sibs of our patient had the same syndrome and died a few days after birth. The other 9 sibs are well, with an unremarkable phenotype. A syndrome of albinism, black lock, deafness, and a total lack of intestinal neural innervation has not yet been reported. It represents a new neural crest syndrome with autosomal-recessive inheritance.

Albinism↗
PubMed1995

Acute and chronic fetal hypoxia in monochorionic and dichorionic twins.

OBJECTIVE: To assess the risk for acute and chronic fetal hypoxia in twin pregnancies. METHODS: We investigated 50 sets of twins (24-38 weeks' gestation, 660-3200 g birth weight) admitted consecutively to our neonatal intensive care unit. Seventy-six infants were appropriate for gestational age (AGA; tenth to 90th percentile), 20 were small for gestational age (SGA; below the tenth percentile), and four were large for gestational age (above the 90th percentile). Twenty-six singleton AGA term newborns served as controls. Umbilical arterial pH was used as a marker for acute and umbilical venous erythropoietin concentration for chronic fetal hypoxia. The results are given as median followed by quartiles. RESULTS: We identified 40 sets of diamniotic-dichorionic twins and ten sets of diamniotic-monochorionic twins with transplacental vascular shunts. In the second-born twin, umbilical arterial pH was lower (7.29, 7.23-7.33) than in the firstborn (7.31, 7.25-7.34) (P = .03), and the incidence of a low pH (less than 7.20) was higher (19 versus 11%). Two second-born twins and none of the firstborn twins had an umbilical arterial pH less than 7.05. In SGA twins, the erythropoietin concentration was elevated (34.8, 22.8-325 mU/mL) compared with that in AGA twins (16.2, 8.2-26.6 mU/mL) (P < .01). In AGA twins, erythropoietin concentration did not differ from that in AGA singleton newborns (19.6, 14.7-31.6 mU/mL). In 12 of 17 twin sets with weight discordancy greater than 15% and in all five twin sets with weight difference greater than 25%, erythropoietin concentration was higher in the smaller twin. The proportion of infants and of complete sets with elevated erythropoietin levels was higher (P < .01) in monochorionic than in dichorionic pregnancies. CONCLUSION: The second-born twin is at increased risk for acute birth asphyxia. Fetal growth restriction in twin pregnancies is associated with chronic fetal hypoxia. Monochorionic twins are at higher risk for chronic fetal hypoxia than are dichorionic twins.

Acute Disease↗
PubMed1995

The neuropsychological spectrum in traumatically head-injured persons.

The neuropsychological spectrum was investigated in a traumatically brain-damaged population. In this spectrum neuropsychological measures were regarded as the most biologically oriented, achievement measures as the most acquired skill-oriented, and intellectual measures as having an intermediate position. It was found that the achievement measures correlated the most highly with each other, the intellectual measures intercorrelated to a lesser extent, and the intercorrelations of neuropsychological measures yielded a zero-order median correlation. It was further found that the correlations of measures with those in other categories had the same ranking. It was inferred that brain damage alters the pattern of the neuropsychological spectrum because of disproportionate impairment in the biological direction of the spectrum.

Achievement↗
PubMed1994

Ion channel properties of the reconstituted chloroplast triose phosphate/phosphate translocator.

The chloroplast triose phosphate/phosphate translocator (cTPT) was isolated from envelope membranes or from transformed yeast cells and reconstituted into artificial membranes. Ionic currents mediated by the cTPT across these membranes were investigated by flux measurements and by the patch-clamp technique. The results of the flux measurements indicate that inorganic phosphate (Pi) at saturating concentrations on both sides of the membrane and chloride (Cl-) at all applied concentrations are transported by the cTPT at rates about 20-fold higher than those measured in intact chloroplasts. After reconstitution of the protein into giant liposomes, single channel currents mediated by the cTPT were resolved with the patch-clamp technique. The protein was shown to be a voltage-dependent anion channel with complex gating revealing sublevels with conductances of 12, 54, 96, and 138 pS for Cl- and 6 pS and 18 pS for Pi, respectively. Recordings from patches compromising multiple channels show a synchronously appearing non-linear current voltage (I/V) relationship in symmetrical buffers, and a different gating at positive and negative membrane potentials. This suggests that the cTPT is incorporated into the membrane in a unidirectional orientation. 3-Phosphoglycerate, a high affinity substrate of the transporter protein, induced a reversible flickering of open channel, and the channel open probability was decreased 60%. It is concluded that, besides its normal counter-exchange mode, the cTPT can also work as a voltage-dependent anion selective channel.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Transfer of the scorpion toxin receptor to an insensitive potassium channel.

Voltage-dependent potassium channels belong to a family of structurally related cation channels that underlie the electrical activity of excitable cells. Many potassium channels are blocked with high affinity by scorpion toxins, whereas others are completely insensitive. We transferred toxin sensitivity from the highly sensitive Kv1.3 (KV3) to the insensitive Kv2.1 (DRK1) potassium channel by transferring the stretch of amino acids between transmembrane domains 5/6. We provide evidence that this S5-S6 linker, which has been shown to comprise the pore-forming region, is probably the only part of the ion channel that directly interacts with bound toxin. Using site-directed mutagenesis, we identified specific residues in the S5-S6 linker that are responsible for the acquisition of toxin sensitivity by Kv2.1.

Amino Acid Sequence↗
PubMed1994

A genetic map of the mouse with 4,006 simple sequence length polymorphisms.

We have constructed a genetic map of the mouse genome containing 4,006 simple sequence length polymorphisms (SSLPs). The map provides an average spacing of 0.35 centiMorgans (cM) between markers, corresponding to about 750 kb. Approximately 90% of the genome lies within 1.1 cM of a marker and 99% lies within 2.2 cM. The markers have an average polymorphism rate of 50% in crosses between laboratory strains. The markers are distributed in a relatively uniform fashion across the genome, although some deviations from randomness can be detected. In particular, there is a significant underrepresentation of markers on the X chromosome. This map represents the two-thirds point toward our goal of developing a mouse genetic map containing 6,000 SSLPs.

Animals↗
PubMed1994

Serial study of the immune response of an individual with exacerbated simple cutaneous leishmaniasis.

The immunological responses of a patient with exacerbated cutaneous leishmaniasis, measured during the course of the disease, are described. Except for skin lesions the patient was healthy and showed no signs of immunosuppression. Three immunological parameters were measured: specific lymphocyte proliferation (LPA), monocyte effector activity (MEA), and antibody levels. LPA was positive early in the course of the disease, became negative as the lesions enlarged, and was positive again as the lesions healed 28 weeks after initiation of the study. In the MEA test, in which the mononuclear cells of the patient were incubated in the presence of Leishmania major promastigotes in a 3-day assay, the number of amastigotes per 100 monocytes remained constant until week 28 and then decreased significantly. Antibody levels remained elevated until week 28 and then decreased to background levels. The results indicate that the cell-mediated immune response parallels the course of the disease while circulating antibodies show an inverse relationship.

Acute Disease↗
PubMed1993

Pursuing the voltage sensor of a voltage-gated mammalian potassium channel.

Ion channels are generally classified as voltage- or ligand-gated channels based upon their ability to respond to a change in the transmembrane voltage or to a specific ligand interaction. The voltage sensor of voltage-gated ion channels is thought to be contained within the fourth putative transmembrane segment, S4, and is characterized by basic residues typically spaced apart. Thus far, a full understanding of all charges contributing to the voltage sensor of voltage-gated potassium channels has been lacking since several neutralization mutants in S4 could not be functionally expressed. By construction of multimeric cDNAs encoding a mammalian RCK1 (Kv1.1) potassium channel, we now report functional expression of all charge neutralizations in the S4 segment, providing a more comprehensive insight into the functioning of the voltage sensor.

Animals↗
PubMed1993

[Hepatitis serological finding "anti-HBc alone", circulating viral DNA and interpretation of findings].

The immunological finding "anti-HBc alone" (without HBsAg, without anti-HBs) leaves open the question of the state of HBV infection it reflects: a transitory stage of an uncomplicated, eventually prolonged but resolving infection, a chronic or a late state of immunity. A finding of this kind is often observed in immunocompromised individuals (e.g. patients on hemodialysis, drug addicts) but also occurs in up to 1% of the Swiss blood donor population. Of 8800 sera tested for HBV marker in a diagnostic laboratory, 153 individuals showed "anti-HBc alone". They were investigated for circulating hepatitis B desoxyribonucleic acid (HBV-DNA) by polymerase chain reaction (PCR). 60 individuals (39%) showed a positive result. Also taking into consideration anamnestic measurements of conventional HBV markers in 95 individuals and consecutive testing for HBV-DNA in 50 individuals, the following conclusions emerged: 1. A positive finding of HBV-DNS by PCR does not necessarily prove an ongoing HBV infection, hence a negative result does not rule it out. Therefore, the indication to test for this parameter is limited for routine use. 2. The finding of "anti-HBc alone" implies that a HBV-infection is still going on until proven otherwise. This not only might be of consequence for the individual involved, but also raises the question of screening of blood donors and of pregnant women for anti-HBc.

Adolescent↗
PubMed1993

Anti-IL-4 diminishes in vivo priming for antigen-specific IL-4 production by T cells.

Treatment of mice with neutralizing monoclonal anti-IL-4 antibodies at the time of immunization with keyhole limpet hemocyanin causes significant inhibition of priming of T cells for the production of IL-4 upon subsequent in vitro challenge. BALB/c mice received a single injection of anti-IL-4 at the time of immunization. T cells purified from spleen and lymph nodes were obtained at 6 to 7 days and at 30 to 75 days after priming. In the 6- to 7-day group, IL-4 production in response to keyhole limpet hemocyanin among the recipients of anti-IL-4 was reduced by more than twofold in four of four experiments, when low density T cells were challenged. In some, but not all, of these experiments, production of IFN-gamma was enhanced at least twofold. Measurement of frequency of IL-4-producing, keyhole limpet hemocyanin-specific T cells indicated a twofold reduction in the anti-IL-4-treated mice. Among cells obtained between 30 and 75 days after priming, production of IL-4 was diminished in four of four cases in high density cells and three of four cases in low density cells. T cells were also prepared from mice that received a secondary in vivo challenge 90 to 105 days after priming. T cells from boosted donors that had received a single injection of anti-IL-4 at the time of priming showed diminished production of IL-4 in each experiment. By contrast, treatment with anti-IL-4 at the time of secondary challenge did not diminish IL-4-producing capacity of cells from mice that were primed in the absence of anti-IL-4. These results indicate that IL-4 is important in vivo in priming T cells to develop into IL-4-producing cells and indicate an important physiologic role for IL-4 in the establishment of lymphokine-producing phenotype.

Adjuvants, Immunologic↗
PubMed1993

Study of the rate of early glucose disappearance following insulin injection: insulin sensitivity index.

The euglycaemic hyperinsulinaemic glucose clamp is usually considered as the reference technique to evaluate insulin sensitivity. As it is an expensive and time-consuming tool, we therefore tried to validate a simple insulin tolerance test (ITT) (IV bolus of 0.1 IU/kg of regular insulin, with glucose sampling at -5, 0, 3, 5, 7, 10 and 15 min) and to demonstrate its usefulness. Insulin sensitivity was measured by DG/G0 ratio (G0 = initial glycaemia, DG is the variation between G0 and the glycaemia obtained at 15 min by the calculation of the regression plot). We confirmed the existence of a correlation between the glucose uptake (mg/kg per min) evaluated by glucose clamp and the DG/G0 index (r = 0.9, P < 0.01). There was no stimulation of hormonal counter regulation during the test. The ITT was significantly correlated both with fasting insulin (r = -0.43, P < 0.01), and post-glucose load insulin concentration (r = -0.67, P < 0.01); each measurement expressing insulin sensitivity. Four groups of patients with different insulin sensitivity: controls, NIDDM, gynoid and android obese subjects, were clearly separated by ITT. We showed that fasting glycaemia and DG/G0 were correlated (y = 2.63/x - 0.093; r = 0.82, P < 0.01). These results suggest that ITT could be an easy, quick and low cost method to evaluate insulin resistance in clinical practice and epidemiological studies.

Adult↗
PubMed1993

Measuring functioning and health in the very old.

To assess the validity of brief multidimensional measures of health, we studied 155 new residents of a long-term care institution. We collected self-reported measures of various aspects of health, as well as performance-based measures of physical and cognitive function. For six similar health dimensions measured using two self-reported methods, the average correlation between paired health dimensions was 0.64 (nonpaired correlation = 0.36). When we compared self-reports and performance on three closely paired health concepts, the average correlation of paired concepts was 0.49 (nonpaired correlation = 0.22). In a factor analysis, similar health dimensions measured using different methods tended to load on the same factor. Except for manual performance, performance-based and self-reported measures of physical and role function loaded on one factor. We conclude that brief measures of health and self-reported physical functioning in very old persons have acceptable validity.

Activities of Daily Living↗