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Biomedical subjects

A Balbo

Publications and source records attributed to A Balbo.

At least 19 recordsLinked to original sources
PubMed2001

Measurement of myo-inositol turnover in phosphatidylinositol: description of a model and mass spectrometric method for cultured cortical neurons.

Rates of myo-inositol (Ins) incorporation and turnover in phosphatidylinositol (PtdIns) were determined in cultured mouse cortical neurons. Cells were incubated with deuterium-labeled myo-inositol (Ins) in culture medium free of unlabeled Ins. The time-dependent changes in the specific activity of cytosolic Ins and membrane PtdIns were measured by mass spectrometry. PtdIns turnover was modeled incorporating values for Ins flux, cytosolic dilution, PtdIns concentration, and rate of incorporation into PtdIns. Recycled Ins diluted the labeled precursor pool, and a time course was obtained for this cytosolic process. The specific activity of the precursor pool at the plateau of the time-course curve was 0.43 +/- 0.04 (mean +/- SD). The incorporation of the tracer into PtdIns was linear between 4 and 10 h incubation of the neurons. After factoring in the extent of dilution of the tracer in the precursor pool, the rate of Ins incorporation into PtdIns was found to be 315 +/- 51 nmol (g of protein)(-1) x h(-1). The half-life of Ins in PtdIns was calculated for each point on the linear incorporation curve and then corrected for the tracer reincorporation. The half-life of Ins in PtdIns was 6.7 +/- 0.2 h, which translates into a basal turnover rate of 10.3%/h in this in vitro system. The mathematical model and the stable isotope method described here should allow assessment of the dynamics of PtdIns signaling altered in certain diseases or by agents.

Animals↗
PubMed2001

Studies on inhibition of human platelet function by sodium nitroprusside. Kinetic evaluation of the effect on aggregation and cyclic nucleotide content.

In this study, we explored the ability of sodium nitroprusside to inhibit the aggregation of human platelets in platelet-rich plasma (PRP) and whole blood and its effects on intracellular levels of guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP). The experiments investigated dose-dependent effects of nitroprusside starting from concentrations in the range of circulating levels achievable in vivo during drug administration in humans. Furthermore, we investigated the time-course of both antiaggregating action and the influence on cyclic nucleotide synthesis. Results showed that sodium nitroprusside inhibited the aggregation induced by adenosine 5-diphosphate (ADP) and collagen starting from concentration as low as 2 micromol/l. The IC(50) value for ADP-induced aggregation in PRP was 18.7+/-2.4 micromol/l. The inhibition of platelet aggregation showed a time-dependent behaviour and was not reversible within 90 min. The accumulation of intraplatelet cGMP in the presence of sodium nitroprusside exhibited a comparable time-course characterized by an early increase, a steady state and a late further increase. The time-course of cAMP synthesis was very similar to that of cGMP. Our data evidenced a long-lasting inhibition of platelet responses by sodium nitroprusside and excluded a desensitization of platelet guanylyl cyclase after 3-h exposure to nitric oxide (NO). Furthermore, they indicated a role of cAMP accumulation in the antiaggregating effects of nitroso donor: the simultaneous increase of intracellular content of cAMP and cGMP can synergize in the reduction of the platelet responses.

Adenosine Diphosphate↗
PubMed2001

Thyroid autoimmunity and infertility.

We aimed to study the prevalence of thyroid autoimmunity in infertile women; to assess whether thyroid autoantibodies were associated with non-organ-specific autoantibodies; and to investigate the influence of this dysfunction on the couples' chances of pregnancy. We assayed serum levels of thyroid stimulating hormone (TSH), free thyroxine, and microsomal and thyroglobulin autoantibodies in 149 infertile women. In patients with serum TSH levels in the hypothyroid or hyperthyroid range and/or with thyroid autoantibodies, we performed thyroid ultrasound examinations and assayed some non-organ-specific autoantibodies. We compared the duration of infertility in infertile patients with normal thyroid (control group), with thyroid abnormalities, and with thyroid autoantibodies in euthyroidism. Thirty infertile patients (20.1%) had thyroid abnormalities. The prevalence of thyroid autoantibodies was 17.4%. In infertile patients with thyroid autoantibodies, we found a poor association with non-organ-specific autoantibodies. Only the women with thyroid abnormalities and ovulatory dysfunction had a mean duration of infertility significantly longer than that of the control group. When the data were analyzed for euthyroid women with thyroid autoantibodies, we found no significant variation in the duration of infertility. Although we found a high prevalence of thyroid autoantibodies in infertile patients, the presence of these autoantibodies per se did not reduce the chance of pregnancy.

Adult↗
PubMed2000

Brain myo-inositol level is elevated in Ts65Dn mouse and reduced after lithium treatment.

The segmental trisomy Ts65Dn mouse is a novel model of Down syndrome (DS). The purpose of this study was to measure brain levels of myo-inositol (ml), N-acetylaspartate (NAA), and other metabolites in Ts65Dn mice using in vivo 1H magnetic resonance spectroscopy (MRS), and to determine whether lithium (Li) treatment alters brain ml level. The ratio of ml over total creatine (Cr), ml/Cr, was significantly elevated (mean change +38%), while NAA/Cr was significantly decreased (mean change -18%) in Ts65Dn mice (n=5) compared with control mice (n= 7). This is consistent with 1H MRS findings in DS human adults. Brain ml/Cr of the entire sample group (n= 12) was reduced (mean change -15%) following Li treatment, supporting the Li-induced ml depletion hypothesis.

Animals↗
PubMed2000

Cell-cell signaling and adhesion in phagocytosis and early development of Dictyostelium.

Cell-cell signaling and adhesion regulate transition from the unicellular to the multicellular stage of development in the cellular slime mold Dictyostelium. Essential gene networks involved in these processes have been identified and their interplay dissected. Heterotrimeric G protein-linked signal transduction plays a key role in regulating expression of genes mediating chemotaxis or cell adhesion, as well as coordinating actin-based cell motility during phagocytosis and chemotaxis. Two classes of cell adhesion molecules, one cadherin-like and the second belonging to the IgG superfamily, contribute to the strength of adhesion in Dictyostelium aggregates. The developmental role of genes involved in motility and adhesion, and their degree of redundancy, have been re-assessed by using novel developmental assay conditions which are closer to development in nature.

Animals↗
PubMed1998

The ultrastructural effects of beta-amyloid peptide on cultured PC12 cells: changes in cytoplasmic and intramembranous features.

The fine structural features of cultured PC12 cells were investigated after treatment for 1, 3, or 5 days with different concentrations of the vascular form of beta-amyloid 1-40 (beta-AP). PC12 cells treated with beta-AP showed time- and concentration-dependent lysosomal system activation and cell toxicity. We observed increases in the number and size of cytoplasmic lysosomes as indicated by increased acid phosphatase reactivity. Some lysosomes were in the form of multivesicular bodies or large residual bodies that appeared to arise by autophagia or by endocytotic uptake. Double-sided plasma membrane invaginations were observed to give rise to increasingly extensive intracytoplasmic vacuolization that was correlated with duration of beta-AP treatment. Freeze-fracture studies of the intramembranous particle (IMP) population in the plasma membrane P-face showed that both control and beta-AP treated cells had two major P-face IMP populations, small-diameter (4-8 nm) IMPs, and large-diameter (> or = 9 nm) IMPs. The larger category of IMPs was found to possess a greater average diameter in the beta-AP treated cells than in the control cells. These IMPs could represent modifications to existing transmembranous receptors, channels, or transducing molecules by the beta-AP. These results demonstrate that beta-AP can induce time- and concentration-dependent ultrastructural changes in PC12 cell membranes.

Amyloid beta-Peptides↗
PubMed1997

Bronchial and bronchoalveolar inflammation in single early and dual responders after allergen inhalation challenge.

To characterize the cellular inflammation at the bronchial and bronchoalveolar levels, we evaluated 43 patients with asthma who were sensitized to house dust mites. On 2 consecutive days patients underwent methacholine challenge and allergen bronchial challenge. In addition, 6, 24, or 72 h after allergen challenge, fiberoptic bronchoscopy with bronchial lavage (BL) and bronchoalveolar lavage (BAL) was performed. Patients belonging to the 6-h, 24-h, or 72-h group were divided further into two subgroups: those with isolated early response to allergen (LAR-), and those with dual response to allergen (LAR+). The percentage of eosinophils and of epithelial cells in BAL fluid was significantly higher in LAR+ than in LAR- patients in the 6-h group (p < 0.05, each comparison), but not 24 or 72 h after (p > 0.05, each comparison). Similarly, the proportion of BL eosinophils was also higher in LAR+ than in LAR- patients, both in the 6-h and in the 24-h group (p < 0.05, each comparison). In addition, increased proportions of BL neutrophils were present in the LAR+ patients belonging to the 24-h group (p < 0.05). Comparing "proximal" = BL vs "distal" = BAL data, we found a significantly higher proportion of epithelial cells in BL compared with BAL, in both LAR- and LAR+ subjects, either 6, or 24, or 72 h after challenge (p < 0.01, each comparison) and increased percentages of BL neutrophils and eosinophils in LAR+ patients (p < 0.05, each comparison), but not in LAR- patients, in the 24-h group. The percentages of BL or BAL macrophages and lymphocytes did not differ significantly among the different patient groups. These data indicate that the development of LAR after allergen inhalation challenge is associated with an early recruitment of eosinophils and with epithelial desquamation in the airways. In addition, after allergen challenge epithelial desquamation is more pronounced in the proximal than in the distal airways, independently of the type of bronchial response.

Adolescent↗
PubMed1996

A fine structural study of the hippocampus and dorsal root ganglion in mouse trisomy 16, a model of Down's syndrome.

Mouse trisomy 16 (Ts16) appears to provide an animal model of Down's syndrome in that a portion of mouse chromosome 16 is syntenic with part of human chromosome 21. Trisomy 21 in human beings leads to the mental retardation of Down's syndrome and in middle age, to some presenile anatomic and clinical features of Alzheimer's disease. Neural tissue from aging Ts16 mice is unavailable, however, as Ts16 mouse embryos die late in utero. We studied these embryos looking at the ultrastructure of neurons from the hippocampus and dorsal root ganglion in normal control mice embryos (diploid) and in Ts16 late embryonic litter mates after day 15 of gestation. The organelles in the Ts16 neurons looked similar to those in control neurons, fixed and processed under similar conditions. No obvious neuropathological structures were observed. These results, when compared to reports on electrophysiological abnormalities of cultured fetal Ts16 neurons and on abnormalities in neurotransmitter markers in the Ts16 fetal brain, lead us to suggest that the mental retardation of Down's syndrome is likely to result from functional and chemical defects not directly related to abnormal neuronal ultrastructure. When related to fine structural studies of transplanted embryonic Ts16 hippocampus which have been maintained for long periods of time, these results indicate that the trisomic mouse brain would not be useful as a structural model for Down's syndrome and hence presenile Alzheimer's disease, as it is not associated with any detectable morphological abnormality.

Action Potentials↗
PubMed1996

Airway eosinophilic inflammation, epithelial damage, and bronchial hyperresponsiveness in patients with mild-moderate, stable asthma.

Allergic asthma is characterized by chronic recruitment of eosinophils in the airways. Once activated, eosinophils release toxic products, including eosinophil cationic protein (ECP), able to damage airway epithelial cells. To test the hypothesis that also in mild-moderate stable asthma, a significant eosinophil activation could occur, we studied 25 asthmatic patients (34 +/- 19 years old), of whom 18 were allergic (27 +/- 12 years) and seven nonallergic (42 +/- 10 years), with FEV1 values > or = 70% of predicted, and eight normal volunteers (controls, 33 +/- 11 years). All subjects underwent methacholine (MCh) challenge on the first visit, and bronchoalveolar lavage (BAL) on the second visit (approximately 3-4 days later). BAL cells were counted and albumin (Alb) (as index of protein dilution in BAL fluid) and ECP levels (as index of eosinophil activation) in BAL fluid were measured. As compared to controls, a significant increase in BAL eosinophil and in BAL epithelial cell numbers was observed in asthmatic patients (P > 0.05, each comparison), with no differences between the two asthmatic patient subgroups. Detectable ECP levels (> 2 micrograms/1) were found in BAL of 18 asthmatic patients (14 allergic and four nonallergic asthmatic patients), while Alb levels were measurable in 25 BAL fluids and found to be similar in controls and asthmatic patients, and in the two asthmatic patient subgroups (P > 0.05, each comparison). In BAL of asthmatic patients, positive correlations were found between eosinophil numbers and 1) ECP/Alb levels (r = 0.50, P = 0.020); 2) epithelial cell numbers (r = 0.50, P = 0.014). In asthmatic patients, a significant negative correlation was found between bronchial reactivity to MCh (log Pd15) and ECP/Alb levels in BAL fluid (r = -0.6, P = 0.005), whereas no correlation was found between log Pd15 MCh and BAL eosinophil or epithelial cell number (P > 0.1, each correlation). These data suggest that bronchial eosinophil recruitment and activation may occur also in mild-moderate stable asthma and that bronchial epithelium damage and airway responsiveness may be partially associated with the eosinophilic inflammatory reaction.

Adolescent↗
PubMed1996

BAL neutrophilia in asthmatic patients. A by-product of eosinophil recruitment?

Although neutrophil number may be increased in the airways of patients with asthma, its pathogenetic role in this disorder remains unclear. We evaluated BAL of 8 normal control subjects, 30 +/- 2 years of age, and 24 patients with mild asthma: 17 patients with allergic asthma, 24 +/- 1 years of age, and 7 patients with nonallergic asthma, 30 +/- 1 years of age. The BAL of asthmatic patients showed increased numbers of neutrophils (p < 0.01), eosinophils (p < 0.01), and ciliated epithelial cells (p < 0.05) and increased concentrations of myeloperoxidase (MPO) (p < 0.01) compared with control subjects. Positive correlations were observed between the number of BAL neutrophils and eosinophils (Rs = 0.780, p < 0.0001) and between BAL neutrophil numbers and BAL MPO levels (Rs = 0.40, p < 0.05). No correlations were found between the following: (1) BAL eosinophils or neutrophils and BAL epithelial cells (p > 0.05, each comparison); (2) BAL neutrophils or eosinophils and log Pd15 methacholine (MCh) (p > 0.05, each comparison); or (3) BAL epithelial cells or log Pd15 MCh and BAL MPO (p > 0.05, each comparison). Dividing the patient population into two groups, allergic asthmatics and nonallergic asthmatics, similar BAL neutrophil, eosinophil, and epithelial cell numbers and similar MPO levels were found (p > 0.05, each comparison). In addition, the correlations between BAL neutrophils and eosinophils showed similar significance in the two patient subgroups (p > 0.05, each comparison). These results suggest that, both in allergic and nonallergic asthma, airway recruitment and activation of neutrophils occur as does parallel eosinophil migration. However, airway neutrophils do not seem to contribute significantly to epithelial cell injury or to airway hyperresponsiveness in the steady state.

Adolescent↗
PubMed1995

Oligoclonality of lung T lymphocytes following exposure to allergen in asthma.

We were interested in studying the lung allergen-specific T cell repertoire in different conditions of allergen exposure in subjects with atopic asthma. Twenty-one allergic individuals were studied: 17 subjects suffering mainly from asthma and 4 from rhinitis. They all performed spirometry and methacholine challenge. All patients were subjected to bronchoalveolar lavage (BAL), either at base line (no challenge) or after allergen or histamine challenge, and the TCR repertoire of their lung T cells was studied with heteroduplex analysis. Expansion of single T cell clones was observed in one (of seven) asthmatic subject that reported a recent exposure to allergen and had high bronchial hypersensitivity to methacholine, and in seven/seven asthmatic subjects who underwent BAL after they suffered an early asthmatic reaction to experimental allergen inhalation. Remarkably, ex vivo expanded clones included allergen-specific T cells. In two of the seven subjects who underwent BAL after allergen challenge, two different lung segments were lavaged. A strikingly symmetrical distribution of the expanded clones was found in these samples. Control subjects and six of seven asthmatic patients studied at base line showed polyclonality of lung T cells. In conclusion, T lymphocytes are clonally expanded in the lower respiratory tract only in asthmatic subjects exposed to allergen. These results suggest that in allergic asthma, the inhalation of sensitizing allergens can recruit to the lung T lymphocytes that include allergen-specific T cell clones.

Adolescent↗
PubMed1994

Long-term intracerebral transplants of fetal hippocampus from mouse trisomy 16, a model for Down's syndrome (trisomy 21), do not exhibit Alzheimer's disease neuropathology by ultrastructural criteria .

Murine trisomy 16 (Ts16) is an animal model for Down's syndrome (human trisomy 21), because mouse chromosome 16 is genetically homologous to human chromosome 21. Down's syndrome patients, older than 35 years, demonstrate the neuropathological and neurochemical defects characteristic of Alzheimer's disease and Ts16 mouse fetuses exhibit phenotypic abnormalities similar to those in Down's syndrome fetuses. Trisomic mouse fetuses, however, die in utero, and so do not survive long enough for their brains to develop the degenerative changes of aging. This can be overcome by grafting the fetal Ts16 hippocampus (an early site for the development of the pathological features characteristic of Alzheimer's disease), into the cerebral ventricle or striatum of a normal adult mouse host. We have made such transplants, which have survived for up to 12 months. Examining these grafts ultrastructurally at various stages from 1 to 12 months, and comparing them with normal control grafts, reveals no structural difference that could be deemed characteristic of Alzheimer disease; no neurofibrillary tangle or senile plaque was observed. These observations, together with the normal structure of the neuronal organelles in trisomic hippocampal tissue, suggest that trisomic mouse grafts are not a useful model for Alzheimer's disease, despite earlier reports to the contrary.

Alzheimer Disease↗
PubMed1994

Bronchial provocation test with allergen: comparison between two different techniques.

Allergen bronchial provocation tests (BPTs) are often used for assessment of treatment efficacy. Usually, the allergen dose provoking a 20% fall of forced expiratory volume in one second (FEV1) (PD20) is determined on a prestudy day, and this single dose is administered for comparisons on study days. The inhalation of allergen may cause both an isolated early asthmatic response (EAR) or, more frequently, an EAR followed by a late asthmatic response (LAR). Whether the method used to elicit EAR, i.e. the inhalation of cumulative doses up to PD20 or the inhalation of a single predetermined PD20, give comparable results has not been established. We have, therefore, compared the results obtained using the two methods. Twelve patients underwent a first BPT with the increasing doses method and a second BPT with a single dose method. EAR, LAR, and allergen-induced increase of methacholine (MCh) sensitivity were compared. Both methods gave similar EAR's and LAR's although EAR tended to be more severe with the increasing dose method than with the single dose method. The ratio of postallergen/preallergen MCh sensitivity was poorly reproducible.

Adult↗
PubMed1993

Long-term transplants of mouse trisomy 16 hippocampal neurons, a model for Down's syndrome, do not develop Alzheimer's disease neuropathology.

Hippocampal tissue from embryonic day 15-17 fetal mice, euploid or trisomic for chromosome 16, was transplanted into the striatum or the lateral ventricle of 6-8 week old female C57B1/6 mice. After 6-14 months of survival, host brains were sectioned and the grafts were examined by histochemical techniques and by immunocytochemistry for antigens present in pathological brain structures of Alzheimer's disease (AD) patients. Nissl-stained grafts contained aggregations of neurons similar to the pyramidal or the granule cell layers of the normal adult mouse hippocampus. No obvious morphological difference was detected between trisomic and control transplants. The monoclonal antibody Alz-50, which recognizes the paired helical filaments characteristic of AD, or an antibody raised to beta-amyloid peptide, did not reveal neurodegeneration in these grafts. Antibodies against ubiquitin, 200 kDa subunit of neurofilament, alpha 1-antichymotrypsin and tau also did not demonstrate AD-type immunoreactivity in the trisomic or control grafts. Thioflavin S- or silver stained-sections were also negative. We conclude that transplanted hippocampal tissue from the trisomy 16 mouse does not represent an animal model for AD-type neurodegeneration. These results differ from those of Richards et al., EMBO J. (10) (1991) 297-303, who reported AD-type degeneration in trisomy 16 hippocampal transplants.

Alzheimer Disease↗
PubMed1993

Is the allergen-inhalation challenge predictive of the severity of seasonal asthmatic exacerbations?

Fifteen asthmatic patients sensitized to Parietaria pollen were studied. Before the pollen season they underwent an allergen-inhalation challenge which was preceded and followed by a methacholine-inhalation challenge. Pollen count, symptom score, and drug consumption were monitored daily throughout the study. A severity score was obtained by adding symptom score and drug consumption. Patients underwent a third methacholine challenge during the pollen season, after they had been exposed to a high atmospheric concentration of pollen. The severity score during the first period of the pollen season was significantly correlated with both the early and the late asthmatic responses to the allergen observed before the season (r2 = 0.50; P < 0.005). Bronchial sensitivity to methacholine was significantly increased both after allergen challenge and after seasonal exposure, but these increases correlated neither with each other nor with the severity score. We conclude that bronchial responses to experimental exposure to allergens, but not the changes in nonspecific airway responsiveness, can, in part, predict the severity of asthma exacerbation during the pollen season.

Adolescent↗
PubMed1992

Airway inflammation and occurrence of delayed bronchoconstriction in exercise-induced asthma.

We studied nine asthmatic patients with a history of exercise-induced asthma (EIA) in order to investigate whether inflammatory changes in the airways occur after exercise and are eventually associated with the development of a late-phase asthmatic response. On two separate study days, bronchoalveolar lavage (BAL), bronchial lavage (BL), and bronchial biopsy (BB) were performed 3 h after an exercise or a methacholine (MCh) challenge. On two other separate occasions, FEV1 was monitored for 12 h after identical exercise and MCh challenges not followed by BAL, BL, and BB. We found a greater percentage of eosinophils in BAL after exercise versus MCh challenge (p < 0.05). In five patients, BAL eosinophils after exercise were > or = 2% of total inflammatory and immunoeffector cells. In three of these patients an FEV1 fall > 20% of control was recorded 5 to 12 h after exercise. However, two of these patients had 2% or more eosinophils in BAL and similar late falls of FEV1 after MCh challenge. The percentage of degranulating mast cells in BB was higher (p < 0.05) after EIA than after MCh, but no significant differences were found in BL histamine and leukotrienes. We conclude that (1) exercise may enhance mast cell degranulation and eosinophilic inflammation of the airways, and (2) a delayed bronchoconstriction after exercise is not specific to EIA but is more likely the result of fluctuations in lung function associated with airway inflammation.

Adult↗
PubMed1991

Blood-nerve barrier in the frog during wallerian degeneration: are axons necessary for maintenance of barrier function?

Blood-nerve barrier tissues (endoneurial blood vessels and perineurium) of the frog's sciatic nerve were studied during chronic Wallerian degeneration to determine whether barrier function depends on the presence of intact axons. Sciatic nerves of adult frogs were transected in the abdominal cavity; the ends were tied to prevent regeneration and the distal nerve stumps were examined. Vascular permeabilities to horseradish peroxidase and to [14C]sucrose increased to day 14, returned toward normal levels by 6 weeks, and continued at near normal levels to 9 months. Perineurial permeabilities to the tracers increased by day 10 and remained elevated at 9 months. Proliferation of perineurial, endothelial, and mast cells occurred between 3 days and 6 weeks, resulting in an increased vascular space (measured with [3H]dextran) and number of vascular profiles. The perineurium increased in thickness and the mast cells increased in number. This study indicates that during Wallerian degeneration of the frog's sciatic nerve there is 1) a transitory increase in vascular permeability distal to the lesion, that is related to changes within the endoneurium; 2) an irreversible increase in permeability of the perineurium, which begins later than that seen in the endoneurial blood vessels; and 3) proliferation of non-neuronal components in the absence of regenerating neuronal elements. The results indicate that maintenance of vascular integrity does not require the presence of axons in the frog's peripheral nerve, whereas perineurial integrity and barrier function are affected irreversibly by Wallerian degeneration.

Animals↗