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A Hasson

Publications and source records attributed to A Hasson.

At least 19 recordsLinked to original sources
PubMed1995

A new family of conotoxins that blocks voltage-gated sodium channels.

Conus peptides, including omega-conotoxins and alpha-conotoxins (targeting calcium channels and nicotinic acetylcholine receptors, respectively) have been useful ligands in neuroscience. In this report, we describe a new family of sodium channel ligands, the mu-O-conotoxins. The two peptides characterized, mu-O-conotoxins MrVIA and MrVIB from Conus marmoreus potently block the sodium conductance in Aplysia neurons. This is in marked contrast to standard sodium channel blockers that are relatively ineffective in this system. The sequences of the peptides are as follows. mu-O-conotoxin MrVIA: ACRKKWEYCIVPIIGFIYCCPGLICGPFVCV mu-O-conotoxin MrVIB: ACSKKWEYCIVPILGFVYCCPGLICGPFVCV mu-O-conotoxin MrVIA was chemically synthesized and proved indistinguishable from the natural product. Surprisingly, the mu-O-conotoxins show no sequence similarity to the mu-O-conotoxins. However, ananalysis of cDNA clones encoding the mu-O-conotoxin MrVIB demonstrated striking sequence similarity to omega- and delta-conotoxin precursors. Together, the omega-, delta-, and mu-O-conotoxins define the O-superfamily of Conus peptides. The probable biological role and evolutionary affinities of these peptides are discussed.

Amino Acid Sequence↗
PubMed1995

Electrophysiological characterization of a novel conotoxin that blocks molluscan sodium channels.

A novel peptide toxin, PnIVB, isolated from the venom of Conus pennaceus blocks voltage-gated sodium current in Aplysia neurons. Complete blockade is obtained at a PnIVB concentration of 80 +/- 2.2 nM and 50% blockade at 16 +/- 0.86 nM. The potency of PnIVB in blocking Aplysia sodium current is four orders of magnitude larger than that of tetrodotoxin. The toxin has no paralytic activity when injected into fish. The rapid blockade of sodium current by PnIVB is not associated with a change in the activation or inactivation kinetics of the current, or with the reversal potential. Sodium current blockade is reversible after a 30 min wash with 50 times the bath volume. The novel conotoxin PnIVB can be used as a powerful tool for mollusc neurobiological research and as a molecular probe to explore the structure-function relations of voltage-gated sodium channel subtypes.

Action Potentials↗
PubMed1995

Alterations of voltage-activated sodium current by a novel conotoxin from the venom of Conus gloriamaris.

1. The novel peptide toxin delta-conotoxin-GmVIA, recently purified by us from the mollusk-hunting snail Conus gloriamaris, induces convulsive-like contractions when injected into land snails but has no detectable effects in mammals. 2. At concentrations of 0.5-0.75 microM, the toxin induces action potential broadening and increased excitability of cultured Aplysia neurons. 3. Whole cell patch-clamp experiments on cultured Aplysia neurons revealed that the toxin does not alter potassium or calcium currents, but induces action potential broadening by slowing the inactivation kinetics of the sodium current. Under control conditions, the inactivation kinetics of the sodium current follows a single exponential with tau = 0.47 +/- 0.14 (SE) ms. After toxin application the sodium current inactivation is composed of two phases: an early phase with tau = 0.86 +/- 0.12 ms and a late phase of slowly inactivating sodium current with tau = 488 +/- 120 ms. In addition, the toxin shifts the voltage-dependent steady-state inactivation curve to more positive values and the steady-state activation curve to more negative values. These alterations are not associated with changes in the rise time or the peak value of the sodium current. 4. The novel delta-conotoxin-GmVIA, and the previously described "King Kong peptide," purified from another mollusk-hunting cone (Conus textile), share a similar cystein framework also found in the calcium channel blocking peptide omega-conotoxin but represent a new class of conotoxins with unusual specificity for molluscan sodium channels.

Action Potentials↗
PubMed1994

Delta-conotoxin GmVIA, a novel peptide from the venom of Conus gloriamaris.

A novel peptide toxin, delta-conotoxin GmVIA, was purified from the venom of Conus gloriamaris, a mollusc-hunting snail. It consists of 29 amino acids, including six Cys residues: [sequence: see text] The pattern of disulfide connectivity (4-19, 12-24, and 18-29) is the same as for the omega-conotoxins, which are Ca2+ channel ligands. However, the peptide does not compete with omega-conotoxin for binding to membrane preparations from frog, rat, and chick brain. Instead, initial electrophysiological results suggest that the peptide induces action potential broadening in molluscan neurons by slowing down Na+ current inactivation. Synthetic delta-conotoxin GmVIA was prepared by solid-phase methods and appeared identical in all respects to the natural material. The chromatographic behavior of native and reduced delta-conotoxins is quite remarkable, suggesting that the disulfides form a core which forces hydrophobic residues to point out toward the solvent.

Amino Acid Sequence↗
PubMed1994

New mollusc-specific alpha-conotoxins block Aplysia neuronal acetylcholine receptors.

Two mollusc-specific neurotoxic peptides from the venom of the molluscivorous snail Conus pennaceus are described. These new toxins block acetylcholine receptors (AChR) of cultured Aplysia neurons. Bath application of 0.5-1 microM toxin induces 5-10-mV membrane depolarization, which recovers to the control level within 1-3 min in the presence of the toxin. This response is blocked by 1 mM hexamethonium. Concomitantly with the transient depolarization, the toxins block approximately 90% of the depolarizing responses evoked by brief iontophoretic application of acetylcholine. The pharmacology and amino acid sequences of the toxins (alpha PnIA, GCCSLPPCAANNPDYC-NH2; alpha PnIB, GCCSLPPCALSNPDYC-NH2) enable their classification as novel alpha-conotoxins. The sequences differ from those of previously described alpha-conotoxins in a number of features, the most striking of which is the presence of a single negatively charged residue in the C-terminal loop. This loop contains a positively charged residue in piscivorous venom alpha-conotoxins. In contrast to other alpha-conotoxins, which are selective for vertebrate skeletal muscle nicotinic ACh receptors, these Conus pennaceus toxins block neuronal ACh receptors in molluscs. As such they are new probes which can be used to define subtypes of ACh receptors, and they should be useful tools in the study of structure-function relationships in ACh receptors.

Amino Acid Sequence↗
PubMed1993

Alteration of sodium currents by new peptide toxins from the venom of a molluscivorous Conus snail.

TxIA and TxIB, peptides with 27-amino acid residues recently isolated from the molluscivorous marine snail Conus textile neovicarius, exhibit strong paralytic activity in molluscs, with no paralytic effects on athropods and vertebrates. At concentrations of 0.25-0.5 microM the toxins cause spontaneous repetitive firing and dramatic broadening of the action potential of cultured Aplysia neurons. The action potential duration partially recovers within 30 min in the presence of the toxins. Under these conditions a second toxin application does not change the spike duration. TxI-induced spike broadening occurs when potassium and calcium conductances are blocked. Voltage-clamp experiments revealed that the toxins alter the kinetics of the sodium current either by slowing down the rate of sodium current inactivation or by recruiting silent sodium channels with slower activation and inactivation kinetics. The toxins shift the voltage-dependent steady-state Na+ current inactivation curve to more positive values by 6 mV. These changes are not associated with alteration in the rate of sodium current activation, in the peak sodium current, or the sodium current reversal potential. TxI apparently represents a new class of conotoxins with an unusual phylogenic specificity and may therefore be useful as a probe for the study of molluscan neuronal sodium channels.

Animals↗
PubMed1993

Chemical and electrophysiological characterization of new peptide neurotoxins from the venom of the molluscivorous snail Conus textile neovicarius: a review.

Three peptide toxins exhibiting strong paralytic activity to molluscs, but with no paralytic effects on arthropods or vertebrates, were purified from the venom of the molluscivorous snail Conus textile neovicarius from the Red Sea. The amino acid sequences of these mollusc specific toxins are: TxIA, WCKQSGEMCNLLDQNCCDGYCIVLVCT (identical to the so-called 'King Kong peptide'); TxIB, WCKQSGEMCNVLDQNCCDGYCIVFVCT; TxIIA, WGGYSTYC gamma VDS gamma CCSDNCVRSYCT (gamma = gamma-carboxyglutamate). There is a similarity of the Cys framework of these toxins to that of the omega-conotoxins; however, their net negative charges, high content of hydrophobic residues, and uneven number of Cys residues in TxIIA are highly unusual for conotoxins. When assayed on isolated cultured Aplysia neurons, all three toxins induced spontaneous repetitive firing. The TxI toxins also induced a marked prolongation of the action potential duration. Voltage clamp experiments revealed that the TxI toxins alter the kinetics of the sodium current either by slowing down the rate of sodium current inactivation, or by recruiting silent sodium channels with slower activation and inactivation kinetics. The toxins shift the voltage-dependent steady-state Na+ current inactivation curve to more positive values by 6 mV. These changes are not associated with alteration in the rate of INa+ activation, in the peak INa+, or the sodium current reversal potential. TxI represents a new class of conotoxins with an unusual phylogenic specificity and may therefore be useful as a probe for the study of voltage gated sodium channels. (This review summarizes previously published papers).

Amino Acid Sequence↗
PubMed1992

Acquired symmetric lipomatosis of the soles. A plantar form of the Madelung-Launois-Bensaude syndrome.

Benign symmetric acquired lipomatosis is a rare condition characterized by multiple, diffuse, subcutaneous collections of nonencapsulated mature adipose tissue. A thick and disfiguring deposit of fat is symmetrically distributed in the subcutaneous tissue of the neck, upper trunk and proximal portions of the upper extremities. The face, distal extremities, hands, and feet are characteristically spared. We describe a case in which only plantar involvement was present.

Adipose Tissue↗
PubMed1991

Mollusc-specific toxins from the venom of Conus textile neovicarius.

Three peptide toxins exhibiting strong paralytic activity to molluscs, but with no paralytic effects on arthropods or vertebrates, were purified from the venom of the molluscivorous snail Conus textile neovicarius from the Red Sea. The amino acid sequences of these mollusc specific toxins are: TxIA, WCKQSGEMCNLLDQNCCDGYCI-VLVCT (identical to the so called 'King Kong peptide'); TxIB, WCKQSGEMCNVLDQNCCDGYCIVFVCT; TxIIA, WGGYSTYC gamma VDS gamma CCSDNCVRSYCT (gamma = gamma-carboxyglutamate). There is a similarity of the Cys framework of these toxins to that of the omega-conotoxins; however, their net negative charges, high content of hydrophobic residues and uneven number of Cys residues in TxIIA, are highly unusual for conotoxins. When assayed on isolated cultured Aplysia neurons, all three toxins induced membrane depolarization and spontaneous repetitive firing. The TxI toxins also induce a marked prolongation of the action potential duration, which is sodium dependent. These effects differ significantly from the blocking activities of piscivorous venom conotoxins. These mollusc specific conotoxins may therefore serve as new and selective probes for ion-channel functions in molluscan neuronal systems.

Amino Acid Sequence↗
PubMed1991

Malignant combined nevus.

This report describes an example of combined nevus with malignant transformation. The clinical impression was blue nevus. Histologically, the lesion was composed of a cellular blue nevus in the reticular dermis and an overlying compound melanocytic nevus. The junctional component of the melanocytic nevus showed transition to malignant melanoma in situ. A review of the literature failed to find a precedent for the present case.

Cell Nucleus↗
PubMed1991

Erythema elevatum diutinum mimicking porphyria cutanea tarda.

A case of erythema elevatum diutinum (EED) closely resembling porphyria cutanea tarda (PCT) is reported. The initial skin biopsies were suggestive for PCT but porphyrin levels in the urine, stool and plasma were normal. A further biopsy from an early cutaneous lesion showed a leucocytoclastic vasculitis with fibrinoid necrosis of the vessel walls.

Adult↗
PubMed1991

Localized epidermal necrolysis (erythema multiforme-like reaction) following intravenous injection of vinblastine.

We report a case of localized epidermal necrolysis that developed 24 hours after an intravenous injection of vinblastine. Clinically, the lesions consisted of erythematous macules, vesicles, and bullae with a linear arrangement over the injected vein. Histologically, the lesions showed features closely resembling erythema multiforme (epidermal necrolysis). We discuss the pathogenesis of this curious cutaneous drug reaction and review the literature concerning local cutaneous complications associated with intravenously administered chemotherapeutic agents.

Erythema Multiforme↗
PubMed1991

Postlymphography linear dermatitis.

Cutaneous effects secondary to lymphography are rare events. We herein report a patient with Hodgkin's disease who developed a linear dermatitis in both lower limbs 6 days after a pedal lymphography. Histopathologic examination of the lesions demonstrated a subacute dermatitis. Patch tests with the substances used in the lymphography yielded negative results. We discuss the possible pathogenic mechanisms of this striking linear dermatitis.

Adult↗
PubMed1991

Linear pemphigus vulgaris along a surgical scar.

A 64-year-old female had breast carcinoma of the right breast, and a mastectomy was performed. Three years later she developed a vesiculobullous eruption along the surgical scar. Histopathological and direct immunofluorescence findings were consistent with a diagnosis of pemphigus vulgaris. We discuss the possible pathogenesis for this striking linear distribution of the pemphigus vulgaris lesions.

Breast Neoplasms↗
PubMed1991

Localized hyperkeratosis lenticularis perstans (Flegel's disease).

A case of hyperkeratosis lenticularis perstans involving only the back of a thirty-nine-year-old woman is reported. Histologic examination showed foci of compact and eosinophilic hyperkeratosis overlying a thinned stratum malpighii. In the underlying papillary dermis there was no evidence of inflammatory infiltrate. This case demonstrates that hyperkeratosis lenticularis perstans may appear as a localized disorder, and that the inflammation is not an essential pathogenic process in this disorder.

Adult↗
PubMed1991

[Cutaneous epithelial necrosis in coma. Study of 2 cases].

We report two cases of epithelial necrosis in comatous patients. The cutaneous lesions were characterized by erythematous plaques which later evolved to bullous lesions. Histologic examination demonstrated epidermal necrosis with subepidermal blisters, sparse neutrophilic inflammatory infiltrate and, characteristically, eosinophilic necrosis of the eccrine sweat gland coils.

Adult↗
PubMed1990

Spring eruption of the ears.

Spring eruption of the ears is a distinctive photo-dermatosis characterized by the onset of papules and vesicles on the light-exposed helix of the ears that usually develop in the early spring months and mainly affect juvenile males. Histologically the picture evolves according to evoluntionary stage of the lesions from a nodular dermal inflammatory infiltrate in papular lesions to subepidermal blisters in vesicles. The striking and isolated location on the ears and its onset as small outbreaks are clinical features resulting from unknown mechanisms.

Adult↗