Biomedical subjects

M F Martin

Publications and source records attributed to M F Martin.

At least 19 recordsLinked to original sources

PubMed1992

The amino acid sequence of toxin IV from the Androctonus australis scorpion: differing effects of natural mutations in scorpion alpha-toxins on their antigenic and toxic properties.

The complete amino acid sequence (64 residues) of the AaH IV toxin from the scorpion Androctonus australis Hector was determined by automated Edman degradation and was compared with the sequences of other Androctonus toxins. AaH IV was also tested by radioimmunoassay for binding to antisera raised against other toxins of the same species. The results indicated that AaH IV shares some of the antigenic properties of AaH I and AaH III toxins, but does not cross-react with anti-AaH II antibodies. The structural basis for the observed antigenic relationships can be found in the high degree of homology displayed by AaH IV with regard to AaH I and III, the changes in amino acid residues equally affecting regions included or excluded from the main predicted antigenic sites of AaH IV. The lower biological potency of AaH IV is presumably the result of some of the sequence differences. In particular, substitution affecting the charge and bulkiness of residue 61 could account for the poor receptor binding and consequential weak toxic properties of this molecule.

Amino Acid Sequence↗

PubMed1992

The effect of age on the caloric requirement of malnourished individuals.

The effect of age on the response to total parenteral nutrition (TPN) was evaluated in 325 patients by measuring body composition by multiple-isotope dilution at the onset and at 2-wk intervals during the course of TPN. On the basis of their initial body composition, patients were divided into two groups: normally nourished and malnourished. TPN did not alter the body composition of the normally nourished patients. In the malnourished patients, a statistically significant correlation existed between the daily change in the dependent variable body cell mass (BCM) and the independent variables caloric intake, nutritional state, and age. With advancing age, more calories are required to maintain the BCM of malnourished patients. With a similar nutritional intake, a depleted BCM is restored more slowly in older patients. Age is a significant independent variable affecting the response to nutritional support.

Adolescent↗

PubMed1992

Systemic lupus erythematosus presenting with myelofibrosis.

The 20-year-old girl we describe presented with myelofibrosis and systemic lupus erythematosus (SLE), which initially responded to treatment with corticosteroids but during a relapse 9 months later a bone marrow biopsy revealed no improvement in her myelofibrosis. As the cytotoxic treatments used to treat severe SLE may be associated with bone marrow suppression, it is important to consider the possibility of myelofibrosis complicating SLE, which, even when it is a presenting feature, may not readily respond to corticosteroids. When this girl was subsequently treated with high dose steroid and azathioprine her myelofibrosis went into remission.

Adrenal Cortex Hormones↗

PubMed1988

The correlation between Na+ channel subunits and scorpion toxin-binding sites. A study in rat brain synaptosomes and in brain neurons developing in vitro.

Photoreactive derivatives of alpha- and beta-scorpion toxins have been used to analyze the subunit composition of Na+ channels in rat brain. In synaptosomes, both types of toxins preferentially labeled (greater than 85%) a component of 34,000 Da and, at a lower level, another component of 300,000 Da. Reduction of disulfide bridges shifted this latter band from 300,000 Da to 272,000 Da but did not modify the migration of the 34,000-Da component. Similarly, two bands were labeled in cultured brain neurons, one at 259,000 Da by alpha-scorpion toxins and the other at 34,000 Da by both alpha- and beta-scorpion toxins. Contrary to what was observed in synaptosomes, in cultured brain neurons reduction of disulfide bridges had no effect on the migration of the labeled high molecular weight component. Labeling of the smaller polypeptide was obtained even when cells were solubilized with sodium dodecyl sulfate immediately after cross-linking which proves that the 34,000-Da component is not a product of proteolysis. Binding sites for alpha- and beta-scorpion toxins, respectively, did not develop in parallel during neuronal maturation in culture: the increase in beta-scorpion toxin-binding site density was lower and later than that for alpha-scorpion toxin. When related to morphological development, the increase in alpha-scorpion toxin-binding sites was correlated to neurite growth, whereas the increase in beta-scorpion toxin-binding sites was associated with the development of chemical synapses. Finally, in cultured neurons, but not in synaptosomes, both the binding of beta-scorpion toxin and the labeling of the 34,000-Da component by beta-scorpion toxin were enhanced by depolarization of the cell membrane.

Affinity Labels↗

PubMed1988

Preparation of a polyvalent antivenom against various Mexican scorpion Centruroides species.

Antisera were obtained from rabbits injected with four different immunogens from the Mexican scorpion Centruroides suffusus suffusus i.e. the crude venom, a telson extract, a toxic fraction obtained from this telson extract by gel filtration and the same toxic fraction subjected to acetylation. The neutralizing capacity of these antisera are compared: it appears that a telson extract can be used instead of the crude venom to produce an efficient antiserum. The immunological properties of ground telsons obtained from three other species of the Mexican scorpion Centruroides (Centruroides noxius, Centruroides limpidus limpidus, Centruroides limpidus tecomanus) are studied with the antisera raised against Centruroides suffusus suffusus immunogens: an almost total cross-neutralization is observed.

Animals↗

PubMed1988

The use of a pharmacological indicator to investigate compliance in patients with a poor response to antirheumatic therapy.

Twenty-six patients with rheumatoid arthritis which was poorly controlled despite high dose D-penicillamine were studied. Compliance was assessed by standard methods (return tablet count and interview). In addition low-dose phenobarbitone was included in the penicillamine formulation as a pharmacological indicator of compliance. Using these techniques incomplete compliance was apparent in 11 patients (42%). All such patients were identified by the pharmacological marker. Only one admitted poor compliance at interview and only six returned more than a few tablets too many. The reason for the high incidence of poor compliance in this selected group is not apparent but it may represent a significant cause of failure with D-penicillamine therapy. The use of low-dose phenobarbitone may have wider applications in the investigation of patients with other conditions who fail to respond adequately to treatment.

Adult↗

PubMed1988

Caloric requirement of the critically ill septic patient.

The caloric requirement of the critically ill septic patient was determined by measuring body composition, by multiple isotope dilution, before and at 2-wk intervals while receiving total parenteral nutrition (TPN) in 86 septic and 57 nonseptic malnourished patients. All patients received a TPN solution containing 25% dextrose and 2.75% crystalline amino acids. The body composition of the nonseptic patients, who received 51.9 +/- 1.5 kcal/kg.day, improved significantly, while that of the septic patients, receiving 46.8 +/- 1.1 kcal/kg.day was only maintained. The relationship between caloric intake and the restoration of a malnourished body cell mass (BCM) was determined for each group by correlating, using multiple linear regression, the mean daily change in the BCM with the caloric intake and the nutritional state, as determined by body composition. According to the resultant regressions, an intake of 35.1 and 50.7 kcal/kg.day was required to maintain the BCM of the septic and nonseptic patients, respectively. To restore a depleted BCM, caloric intakes in excess of this amount are required.

Aged↗

PubMed1987

Purification and chemical and biological characterizations of seven toxins from the Mexican scorpion, Centruroides suffusus suffusus.

Seven polypeptides highly toxic to mice were isolated from the venom of the scorpion, Centruroides suffusus suffusus (Css), and their chemical and toxic properties were characterized. It was shown that the most active toxins by intracerebroventricular injection are less active when injected subcutaneously. The complete amino acid sequence (66 residues) of toxin II (Css II) has been determined. The C-terminal end is amidated as found for most other scorpion toxins. Css II is a beta-type toxin, previously used to define the binding site for activation of the sodium channel. Using rat brain synaptosomes, we demonstrated that all Css toxins compete with 125I-Css II to bind to site 4 and should be considered as beta-scorpion toxins. Specific binding parameters for Css VI, one of the most active toxins, were determined: KD = 100 pM; capacity in binding sites, 2.2 pmol of toxin/mg of synaptosomal protein. Css VI was shown to inhibit gamma-aminobutyric acid uptake by synaptosomes: K 0.5 = 100 pM, which agrees with its KD. Competition experiments between the seven Css toxins and 125I-Css II for antiserum raised against Css II demonstrated that all these toxins have common antigenic properties.

Amino Acid Sequence↗

PubMed1987

Characterization of six toxins from the venom of the Moroccan scorpion Buthus occitanus mardochei.

When the venom of the Moroccan scorpion Buthus occitanus mardochei was submitted to a combination of several chromatographic steps (including gel-filtration and ion-exchange chromatographies), seven proteins were obtained, six being lethal to mice. These proteins have been characterized by their chemical, immunological and toxic properties. The amino acid sequence (66 residues) of Bom III, the most noteworthy toxin of the venom as for its amino acid composition, is proposed following automatic sequencing of the reduced and S-methylated protein and of chymotryptic peptides. It was obvious that this sequence is somewhat different from those of toxins belonging to the same structural and immunological group (Bom III was found to be immunologically related to Buthus occitanus tunetanus toxins I and II which both share with it 56% of homology. Furthermore, Bom III was found to be unable to compete (as does Bot I) with toxin II of Androctonus australis Hector (an alpha-type toxin) for neurotoxin binding site 3 on the sodium channel of rat brain synaptosomes. Bom III was also unable to compete with toxin II of Centruroides suffusus suffusus (a beta-type toxin) to neurotoxin binding site 4 of the same channel.

Amino Acid Sequence↗

PubMed1987

Use of high performance liquid chromatography to demonstrate quantitative variation in components of venom from the scorpion Androctonus australis Hector.

Using reverse-phase high performance liquid chromatography (RP-HPLC), to resolve less than 1 mg of scorpion venom, quantitative variations in protein components were demonstrated in Androctonus australis Hector venoms obtained either by electric or manual stimulation. The results support polymorphism of scorpion venom components at an individual level.

Animals↗

PubMed1987

Amino acid sequence of toxin XI of the scorpion Buthus occitanus tunetanus. Evidence of a mutation having an important effect upon neurotoxic activity.

The complete amino acid sequence of toxin XI of the North African scorpion Buthus occitanus tunetanus has been elucidated by automatic sequencing of the reduced and alkylated toxin and of the peptides obtained after tryptic cleavage restricted to arginyl bonds. This toxin is structurally homologous to toxin II of Androctonus australis Hector, the most active among the alpha-toxins, but is far less potent, both in vivo and in vitro. This work points out 12 mutations, many of which are conservative. Nevertheless, the most striking difference is the replacement of the lysine residue at position 58, known to be important in the activity of AaH toxin II, by a valine residue. Thus, it seems that the presence of a positive charge at this location facilitates the interactions between the receptor on the sodium channel and the alpha-type toxins.

Amino Acid Sequence↗

PubMed1986

Tityus serrulatus toxin VII bears pharmacological properties of both beta-toxin and insect toxin from scorpion venoms.

Some beta-toxins from the South American scorpion Tityus serrulatus (e.g. Ts VII) are highly toxic both for mouse and fly larva. Radioiodinated Ts VII and the insect toxin from the North African scorpion Androctonus australis Hector (AaH IT) bind to the same site on a house fly head synaptosomal fraction. These results reinforce the hypothesis about the existence of a correlated series of scorpion toxins as previously defined by amino acid compositions and sequences, and immunological and circular dichroism studies, in suggesting that Ts VII constitutes a link which may fill the pharmacological gap existing between beta-toxins and insect toxins such as AaH IT.

Animals↗

PubMed1986

Large scale purification of toxins from the venom of the scorpion Androctonus australis Hector.

A large scale procedure for purification of the toxins in the venom of the North African scorpion Androctonus australis has been developed. This procedure optimizes the sequence of the steps, leading to better yields of toxins and shortening of the time. It is possible to use 10-15 g batches of venom and also prevent cross-contamination of the toxins. High pressure liquid chromatography has been used to separate AaH I and I', two isotoxins which differ by one amino acid residue in position 17: valine or isoleucine. The procedure allows the characterization of a new toxin active in mice, AaH IV, which represents 0.6 and 2.5% of the venom weight and toxicity, respectively. This new component has been characterized as an alpha toxin made up of 61 amino acid residues and having a neutral isoelectric point.

Amino Acids↗

PubMed1985

An excitatory and a depressant insect toxin from scorpion venom both affect sodium conductance and possess a common binding site.

Two insect selective toxins were purified by gel-permeation and ion-exchange chromatographies from the venom of the scorpion, Leiurus quinquestriatus quinquestriatus, and their chemical and pharmacological properties were studied. The first toxin (LqqIT1) induces a fast excitatory contraction paralysis of fly larvae and is about 40 times more toxic than the crude venom. It is a polypeptide composed of 71 amino acids, including 8 half-cystines and devoid of methionine and tryptophan, with an estimated molecular weight of 8189 and a pI value of 8.5. The second toxin (LqqIT2) induces a slow depressant, flaccid paralysis of fly larvae. It is composed of 72 amino acids, including 8 half-cystines, is devoid of proline methionine and histidine, and has an estimated molecular weight of 7990 and a pI value of 8.3. The contrasting symptomatology of these toxins is interpreted in terms of their effects on an isolated axonal preparation of the cockroach in current and voltage clamp conditions. LqqIT1 (0.5-4 microM) induced repetitive firing of the axon which was attributable to two changes in the sodium conductance, a small increase in the peak conductance and a slowing of its turning off. LqqIT2 (1-8 microM) caused a blockage of the evoked action potentials, attributable to both a strong depolarization of the axonal membrane and a progressive suppression of the sodium current. Neither toxin affected potassium conductance. The two toxins differ mainly in their opposite effects on the activatable sodium permeability. In binding assays to a preparation of insect synaptosomal membrane vesicles, the two toxins were shown to competitively displace the radioiodinated excitatory insect toxin derived from the venom of the scorpion, Androctonus australis [( 125I]AaIT), which strongly resembles, in its chemistry and action, the LqqIT1 toxin. The present two toxins have demonstrated a strong affinity closely resembling the AaIT, with KD values of 0.4, 1.9, and 1.0 nM for LqqIT1, LqqIT2, and AaIT, respectively. These data suggest the possibility that the excitatory and depressant insect toxins share a common binding site associated with sodium channels in insect neuronal membranes.

Amino Acids↗

PubMed1985

Effect of dazoxiben, a thromboxane synthetase inhibitor on skin-blood flow following cold challenge in patients with Raynaud's phenomenon.

The effects of dazoxiben on finger-blood flow in response to cold challenge were studied in normal subjects and patients with Raynaud's phenomenon. In normal subjects concentrations of TXB2 and 6-oxo-PGF1 alpha were measured in blood taken from dorsal hand veins following cold challenge. In a parallel multicentre study we examined the effects of dazoxiben on finger temperature and capillary blood cell velocity in patients with Raynaud's phenomenon. Dazoxiben did not affect finger arterial inflow at rest or during cold challenge in patients or controls. However in both groups, recovery was quicker after cold challenge on dazoxiben treatment. In patients median flow was 5 ml (100(-1) ml) min-1 (range 1-10) v. 2 (0.5-15), P less than 0.05 dazoxiben v. placebo at 15 min after cold challenge. However, in normal subjects this did not prove to be statistically significant. In normal subjects there was a fall in TXB2 concentrations and relative rise in 6-oxo-PGF1 alpha following dazoxiben treatment indicating redirection of prostaglandin endoperoxides towards synthesis of PGI2. Comparison of the sum-total output of each eicosanoid following treatment with dazoxiben revealed a 65% reduction in TXB2 concentrations (P less than 0.025 compared with placebo) and a 40% increase in 6-oxo-PGF1 alpha concentrations (P less than 0.05 compared with placebo). However a simultaneous increase in concentrations of FPA indicated generation of thrombin, probably at the needle tip. Long-term treatment with dazoxiben resulted in no significant change in finger-skin temperature or capillary blood cell velocity, duration, or severity of attacks of Raynaud's phenomenon.

6-Ketoprostaglandin F1 alpha↗

PubMed1985

Biochemical and clinical changes occurring during the treatment of rheumatoid arthritis with novel antirheumatoid drugs.

Groups of 15 patients with active rheumatoid arthritis have been treated with sulphasalazine, (salazosulfapyridine INN), zinc sulfate, captopril or methyl cysteine, and assessed by seven clinical measurements and six laboratory methods on eight occasions during a 24-week treatment period. The results have been compared with equivalent data derived from the use of antiinflammatory agents (e.g. aspirin) and drugs of accepted 'antirheumatoid activity' (e.g. D-penicillamine). Improvements in mean data provide the basis of a human screening system for the detection of antirheumatoid drug activity. Results suggest that sulphasalazine and captopril have this type of activity whereas zinc sulfate and methyl cysteine do not.

Adult↗

PubMed1984

Amino acid sequence of toxin VII, a beta-toxin from the venom of the scorpion Tityus serrulatus.

The sequence of the 61 amino acids of toxin VII, a beta-toxin from the venom of the South American scorpion Tityus serrulatus, has been determined by automatic sequencing of the reduced and S-[14C] carboxymethylated protein and of tryptic peptides obtained before or after citraconylation of this protein. This toxin, the most active beta-toxin from this venom, is the first Tityus toxin to be fully sequenced. The results clearly show that toxin VII belongs to the structural group of scorpion toxins originating from Central and North America.

Amino Acid Sequence↗

PubMed1984

Captopril: a new treatment for rheumatoid arthritis?

Captopril, an inhibitor of angiotensin converting enzyme, is prescribed for hypertension. Its molecular structure shares features with D-penicillamine, in that both agents contain a thiol group. In addition, captopril has immunosuppressant activity. Captopril was therefore considered a potential slow-acting drug for treating rheumatoid arthritis. In an open study 15 patients with active arthritis were treated with captopril and followed for 48 weeks. Two-thirds of the patients reported improved arthritis symptoms, and significant changes were seen in several clinical and biochemical measurements, notably Ritchie articular index, clinical score, plasma viscosity, and C-reactive protein. Side-effects were generally mild and included transient taste loss, rashes, and hypotension. Only 2 patients withdrew as a result of drug intolerance.

Adult↗