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G Alroy

Publications and source records attributed to G Alroy.

At least 19 recordsLinked to original sources
PubMed1997

Modulation of endogenous firing patterns by osmolarity in rat hippocampal neurones.

1. Intracellular recordings in adult rat hippocampal slices were used to investigate the modulation of endogenous neuronal firing patterns by moderate changes (+/-13%) in the extracellular osmotic pressure (pi o). The responses of CA1 pyramidal cells to graded depolarizing current pulses were used to differentiate between regular and burst-firing patterns and to characterize the stimulus requirements for evoking endogenous burst discharge. 2. Decreasing or increasing pi o had no significant effects on resting membrane potential and input resistance, spike threshold and amplitude, and the amplitudes of the fast, medium and slow spike after-hyperpolarizations (AHPs). The apparent membrane time constant (tau m) increased in low pi o and decreased in high pi o. 3. Reducing pi o converted non-bursting neurones (non-bursters) to bursting neurones (bursters) and decreased the stimulus requirements for evoking burst firing in native bursters. Increasing pi o suppressed endogenous burst firing. 4. Lowering pi o increased the size of the 'active' (i.e. re-depolarizing) component of the spike after-depolarization (ADP). Conversely, increasing pi o suppressed the active ADP component. 5. The sensitivity of spike ADPs and firing patterns of pyramidal cells to the changes in pi o persisted also in Ca(2+)-free saline, indicating that the osmotic effects are not imparted by modulation of Ca2+ and/or Ca(2+)-activated K+ currents. 6. Blocking most K+ currents with Ca(2+)-free, TEA-containing saline induced large and prolonged (up to 1 s), TTX-sensitive plateau potentials following the primary fast spikes. These potentials were augmented by low pi o and abated by high pi o. 7. When injected with subthreshold depolarizing current pulses in Ca(2+)-free saline, pyramidal cells displayed a distinct TTX-sensitive inward rectification. This rectification was augmented by low pi o and reduced by high pi o. 8. The various effects of low-pi o and high-pi o saline solutions were reversible upon washing with normosmotic saline. 9. We conclude that pi o is a critical determinant of the endogenous firing patterns of CA1 pyramidal cells. The data suggest that the osmotic effects are most likely to be mediated by changes in the persistent Na+ current, which underlies the active spike ADP and the burst potential in CA1 pyramidal neurones. The possible contribution of these effects to changes in brain excitability in various abnormal osmotic states in discussed.

Action Potentials↗
PubMed1994

Menstrual asthma: use of a gonadotropin-releasing hormone analogue for the treatment of cyclic aggravation of bronchial asthma.

A new clinical indication for GnRH-a treatment seems to exist in addition to the many indications known so far. The successful treatment of cyclic severe attacks of bronchial asthma during ovulation and the menstrual periods with a GnRH-a is described. A 45-year-old woman with long-standing bronchial asthma was hospitalized because of severe bronchial asthma and status asthmaticus 11 times during the 5 months before her referral. The hospitalizations were either during the ovulatory or menstrual period, and in two of them they were so grave to require artificial ventilation through an endotracheal tube. To induce pituitary-ovarian desensitization and amenorrhea, the patient was put on monthly injections of depot GnRH-a, which she has been receiving for the last 20 months. Subjective improvement was accompanied by a significant improvement in spirometric indices, by lack of hospitalizations, and decrease in glucocorticoid daily dosage. Although a trial of sequential add-back HRT was unsupportable because of respiratory aggravation, low-dose continuous HRT was tolerated by the patient. In light of the dramatic subjective and objective improvement in association with the GnRH-a treatment, we conclude that this new application deserves further experience.

Asthma↗
PubMed1993

Bronchiolitis obliterans organizing pneumonia. Diagnosis by transbronchial biopsy.

Transbronchial biopsy (TBB) has been considered to be inadequate for the diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP). We describe herein two patients with interstitial pulmonary disease in whom the diagnosis of BOOP was achieved by TBB. The two patients presented with progressive dyspnea, cough, tachypnea, and fine end-inspiratory crackles. The radiologic findings disclosed patchy alveolar infiltrates. Pulmonary function tests showed a restrictive pattern and decreased diffusing capacity. The pathologic findings disclosed bronchioles, alveolar ducts, and alveoli infiltrated with mononuclear cells. The lumina were obliterated with fibroblasts and loose granulation tissue. Corticosteroid treatment resulted in significant improvement. Transbronchial biopsy should be considered as a useful diagnostic tool for BOOP.

Adolescent↗
PubMed1991

Monoclonal antibodies to the heavy neurofilament subunit (NF-H) of Torpedo cholinergic neurons.

Previous studies from our laboratory suggest that Alzheimer's disease sera contain a repertoire of antibodies to the heavy neurofilament subunit (NF-H) and that a subpopulation of these antibodies bind specifically to epitopes highly enriched in NF-H isolated from the purely cholinergic electromotor neurons of Torpedo. In the present study, we prepared and characterized monoclonal antibodies (MAbs) that bind to epitopes specifically enriched in Torpedo cholinergic neurons. This was performed by a differential enzyme-linked immunosorbent assay (ELISA) in which MAbs were selected that bind to epitopes much more abundant in the NF-H protein of Torpedo cholinergic neurons than in NF-H from the chemically heterogeneous Torpedo spinal cord. This yielded four MAbs, three of which (TC4, TC8, and TC21) were found to be specific to NF-H and one (TC15) that reacts with both NF-H and the medium-size neurofilament subunit NF-M. Dephosphorylation abolishes the binding of MAbs TC4 and TC15 to Torpedo cholinergic NF-H, partially reduces that of MAb TC21 and has no effect on the binding of MAb TC8. This suggests that the antigenic sites specific to Torpedo cholinergic NF-H contain phosphorylated as well as non phosphorylated epitopes. All the MAbs cross-react with rat brain NF-H.

Animals↗
PubMed1991

Anti-neuronal antibodies similar to those found in Alzheimer's disease induce memory dysfunction in rats.

Although the etiology and pathogenesis of the cholinergic degeneration in Alzheimer's disease are not known, several reports implicate immunological mechanisms. Recently we have shown that sera of Alzheimer's disease patients contain antibodies which bind specifically to the heavy molecular weight neurofilament protein of Torpedo cholinergic neurons. In the present study we investigated the possibility that such antibodies play a role in neuronal degeneration by examining the behavioral and cellular effects of immunizing rats with the heavy neurofilament protein of Torpedo cholinergic neurons. The immunized rats developed antibodies which were specific to the heavy neurofilament protein of Torpedo cholinergic neurons and which cross-reacted with rat brain neurofilaments. Immunohistochemical studies revealed the accumulation of antibodies in the perikarya and neurites of neurons in the septum and hippocampus of the cholinergic neurofilament immunized rats and in white matter tracts in their forebrains. No such staining was seen in adjuvant immunized control rats. Behavioral tests revealed that rats immunized with the heavy cholinergic neurofilament protein performed significantly worse than controls in a T-maze alternation test and that their performance deteriorated profoundly after the introduction of a 20-s delay in the paradigm, indicating a deficit in short term memory. In contrast, both groups performed similarly in a T-maze discrimination test, indicating that long term reference memory was not affected by immunization with the heavy cholinergic neurofilament protein. Further experiments revealed that the rats immunized with the heavy cholinergic neurofilament protein were also deficient in a reversal of choice paradigm in a position discrimination test.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1991

Characterization of an experimental autoimmune dementia model in the rat.

Alzheimer's disease (AD) and other age-related cognitive deficits are associated with autoimmune phenomena. We recently showed that AD sera contain IgG that binds specifically to the heavy molecular weight neurofilament protein (NF-H) of Torpedo cholinergic neurons. We presently examined the behavioral effects of the induction of such antibodies in rats by prolonged immunization with Torpedo cholinergic NF-H. Immunohistochemical studies revealed the accumulation of IgG in the septum and hippocampus and in white matter tracts of these rats. T-maze alternation and discrimination tests revealed that immunization impaired the short-term working memory of the rats but had no effect on their reference memory. This impairment in short-term memory was reversed by treatment with the acetylcholinesterase inhibitor physostigmine. This animal model, termed experimental autoimmune dementia (EAD), may replicate immunologically induced pathogenic processes in AD.

Alzheimer Disease↗
PubMed1990

Total digoxin-like immunoreactive factor(s) in healthy population, uncomplicated term pregnancies and neonates.

Free digoxin-like immunoreactive factor(s) (DLIF) which may have a homeostatic role, as documented in different physiological conditions, but is generally undetectable in plasma from normal population. Total digoxin-like immunoreactive factor(s) (protein bound and free) can be estimated after plasma is heated. In this study, total digoxin-like immunoreactive factor(s) as measured in plasma in a well defined control population and compared to healthy term pregnant women and neonates, categories known to be associated with increased free digoxin-like immunoreactive factor(s) concentrations. The mean level of this factor(s) in the control group was 706 +/- 129 pg digoxin equivalent/ml (pg/ml) and was unaffected by age and sex. Significantly increased levels of total digoxin-like immunoreactive factor(s) were found in pregnant women and neonates (928 +/- 127 and 1242 +/- 367 pg/ml, respectively). We conclude that levels of total digoxin-like immunoreactive factor(s) are increased in term pregnancies and neonates, similarly to its free form. However total digoxin-like immunoreactive factor(s) is detected in the normal population as a plasma component, contrary to its free form, which is generally undetectable.

Adult↗
PubMed1989

Immunization of rats with cholinergic neurons induces behavioral deficits.

We have previously shown that sera from patients with Alzheimer's disease (AD) contain a significantly high level of antibodies to the cell bodies (Perikarya; PK) but not to the nerve terminals (synaptosomes) of purely cholinergic neurons from the electric fish Torpedo. In the present study we examined the effect of repeated immunization of rats with either of these antigens for one year. Immunoblot studies revealed that sera of cholinergic PK immunized rats contained a high level of antibodies to cholinergic PK proteins, in particular to a 200 kilodalton protein, to which there are specifically high levels of antibodies in AD. Sera from rats immunized with cholinergic synaptosomes and from control rats contained very low levels of these antibodies. Behavioral studies performed one year after the initial immunization revealed that the cholinergic PK immunized rats were impaired in spatial learning and memory tasks (Morris swim test and T-maze alternation) when compared to control rats and that the synaptosome-immunized rats showed no such deficit. In contrast, the three groups performed similarly in general activity, active avoidance and conditioned emotional response tests. Further experiments revealed that the cholinergic PK immunized rats displayed a significant deficit in short term memory. The association of antibodies to cholinergic neurons with cognitive deficits in this rat model suggests that such antibodies may be involved in the pathogenesis of AD.

Acetylcholinesterase↗
PubMed1988

Small intestinal myeloid metaplasia.

Extramedullary hematopoiesis is rarely found in the gastrointestinal tract. A patient with postpolycythemic myeloid metaplasia who previously underwent splenectomy presented with recurrent, protracted gastrointestinal tract hemorrhage. Elaborate workup failed to reveal the source of bleeding. Intraoperative endoscopy with transillumination disclosed multiple submucosal lesions along the entire small bowel, which proved to be extramedullary hematopoiesis. After institution of hydroxyurea therapy, the rate of bleeding diminished considerably.

Aged↗
PubMed1988

Immunological studies of pancytopenia in visceral leishmaniasis.

We report three cases of combined anemia, neutropenia and thrombocytopenia in patients with visceral leishmaniasis (kala-azar). Using immunofluorescence techniques and the common antiglobulin (Coombs') test, we showed membrane-associated antiplatelet, antineutrophil and antierythrocytic IgG antibodies in all three cases. Treatment with sodium stibogluconate raised the patients' platelet, neutrophil and erythrocyte count. At that time no antibodies were detected on peripheral blood cells. Immunological studies performed on these patients did not show marked abnormalities except for reduced T-helper cells and elevated OKM1-positive cells, which normalized after recovery. As bone marrow suppression was not found, it is suggested that pancytopenia resulted from rapid destruction of antibody-coated blood cells. Whether these antibodies are specific is not clear.

Adolescent↗